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Heptyl methacrylate
Fragrance raw materials monograph s
SI13
HEPTYL METHACRYLATE Synony m : Methacrylic acid, hept yl ester. CAS Registr y Number: 5459-37-0 CAS Registr y Name: 2-Pro penoic acid, 2-methyl-, hept yl ester Structure:
~
~H2
CH3-- (CH2) 6-- O-C-C-CH3
Nat ural occurrence: Ha s appa rently not been reported to occur in nature. Volume of use: The worldwide volume of use (1996) as a fragr an ce ingredient is less than I metric ton .
Biological data Acute tox icity Oral studies: Th e o ral LD so in SPF- albin o, Fullinsdorf mice was repo rted to be grea ter than 8 g/kg based on no deaths in 10 animals tested a t that dose after 10 days. Clinical signs of hypom otilit y a nd respiratory depression were observed only du ring the first 3 da ys after treatm ent (RIF M, 1978a). Int raperitoneal studies: Th e LD so by the ip route in SPF-a lbino, Fullinsdorf mice was reported to be greater than 4 g/kg based on 0/10 death s at that dose but less than 8 g/kg based on 10/10 deaths at that dose after 10 days. Clinical signs includ ed ataxia and respiratory depr ession ; death was caused by respirat ory insufficiency by the second da y afte r treatm ent (RIFM, 1978a). Based on these high do ses, no further acute to xicity studies were con sidered appro priate. Skin irritation Human st udies: No irrita tion was observed after a 48-hr closed patch test with 2% in petrolatum on the backs of2 5 health y, male and female volunteers (RIF M, 1985). Animal studies: In a n open epicutan eous test (Kleca k et al.. 1977) on guinea pigs, 3% hept yl methacr ylate in ethan ol was the highest non-irr itat ing concentration after single and repeated applications over 21 da ys; 10% and 30% in ethanol and the neat liquid all produced irrit at ion after a single application ; slight irritation was produced after repe ated applications with 10%; moderate to strong irritation was produced after repeated applications with 30% and the neat liquid (RIFM, 1978b). Mu cous membrane (eye) irritation Animal studies: A rabbit eye test was conducted in three ra bbits with undiluted heptyl meth acrylate. A O.I-ml aliq uot of the neat liquid was applied to the surface of one eye of each rabbit. The untreated eye of each rabbit served as a cont rol. Observat ion s were made immediately after instillation, and a t 1, 24, 48 a nd 72 hr and aga in a t 7 and 14 days. Sco res were recorded accord ing to the Draize scale for scoring ocular lesion s. Some red vessels in the conj unctiva of the eye of one rabbit was observed a t 24 and 48 hr, which clear ed by 72 hr. No altera tion of the co rnea was o bserved macroscopically (RIFM, 1978c). No irritation was observed in rabbi ts (three/dos e) after a O. l-ml aliquo t of either a 10% or 30% solut ion of heptyl metha crylate in dieth yl phthalate was applied to the surface of one eye of each rabbi t. The untreated eye of each rabbit served as a control. Scores were record ed acco rding to the Draize scale for scoring ocular lesion s. Observations were made of the eyes immediately after instillat ion , and at I, 24, 48, 72 hr and aga in at 7 and 14 days (RIFM, 1978c). Skin sensitization Human stu dies: A ma ximizat ion test (Kligma n, 1966; Kligman a nd Epstein, 1975) was carried out with 2% in petrolatum on 25 health y, male a nd female volunteers. Th e test concentration of 2% was based o n a repor ted maximum use concentra tion of 0.2% in con sumer produ cts. Application was under occlusion to the same site on the forea rms of all subjects for five altern ate-day 48-hr period s. Patch sites were pretrea ted for 24 hr with 5% aqueous sodium lau ryl sulfate (SLS) under occlusion for the initial pat ch only. Following a 1014-day rest period challenge pat ches were applied to fresh sites for 48 hr. Challenge appli cat ion s were preceded by 30-min applications of 7.5% aqueous SLS under occlusion on the left side whereas the test material
c. S. Letizia et 01.
SI14
was applied without SLS treatment on the right side. A fifth site challenged with petr olatum served as a control. No react ions were observed that were considered significa ntly irritant or allergic (RIF M, 1985). Animal studies: Six guinea pigs were tested in an open epicuta neous test (Klecak et al., 1977). A to tal of 21 daily induction applications at co ncentrations of 3%, 10% and 30% in ethanol and the neat liquid were followed 14 days later by an open challenge application with the non-irritating concentrat ion of 3% heptyl methacrylate in ethanol. There were no reactions to challenge in any of the experimental groups and it was conclud ed that heptyl methacrylate does not sensitize the guinea pig in this test procedure (R IFM, 1978b). Gu inea pigs (eight/dose) were tested in a Freund's compl ete adjuvant (FCA) test (Klecak et al., 1977) with induction via five intradermal injectio ns of a O.I-ml aliquot of a 5% emulsion of hept yl meth acrylate in FCA on days 0, 2, 4, 7 and 9. Induction was followed on days 21 and 35 with a topical cha llenge using the nonirritating concentration s of I% and 3% . Positive sensitization reactions were observed with 3% heptyl meth acr ylat e in 4/8 guinea pigs at 21 days and in 8/8 at 35 days; 1% hept yl meth acrylat e produced no sensitizat ion reactions (0/8) at 21 days and 1/8 reaction s at 35 days. It was concluded that heptyl methacrylate was a moderat e sensitizer for the guinea pig in the FCA test (RIFM, 1978d). Photo tox icity Anim al studies: No phototoxic properties were observed with heptyl methacrylate (concentration not specified) when applied to the skin of four albino guinea pigs per group for a 48-hr patch test. 4 hr after removal of the pat ch , the skin was irradiate d with either UVA (320-400 nm) for 30 min (Westinghouse FS 40 Black Lamp ) or with UVB (280-3 70 nm) irra dia tion for 15 min (Westingho use FS 40 Sunlamp ) (RIF M, 1978e).
Status Canadian Domestic Subst ances List European Inventory of Existing Commercial Chemical Sub stances Indicative Non-Exhaustive List TSCA Inventory List
Registered Registered 226-727-5 Listed Registered
References Klecak G ., Geleick H . and Frey J .R . (1977) Screening of fragr ance mat erials for allergenicity in the guinea pig. I. Comparison of four testing methods. Journal of the Society of Cosmetic Chemists 28, 53-64. Kligman A.M. (1966) The identification of co ntact allergens by hu man assay. III. The maximization test. A procedur e for screening and ra ting contact sensitizers. Journal of Investigative Dermat ology 47, 39J-409 .[Submitte d only for the methodo logy] Kligman A.M . and Epstein W. (1975) Updating the maximization test for identifying contact allergens. COil tact Dermatitis 1, 231- 239.[Submitted only for the meth od ology] Resear ch Institute for Fr agrance Materials, Inc. (l978a) Acut e toxicity studie s. Un published report from Roure Incorporat ed, 16 May. Report numb er 2180. Resear ch Institut e for Fragran ce Materi als, Inc. (1978b) Skin irritation and capac ity of allergenic sensitizat ion determined by the o pen epicutaneous test (OET) o n guinea pigs. Unpublished report from Roure Incorp orat ed, 25 Jan uary. Report numb er 2 178. Research Institute for Fragrance Ma terials , Inc. (l978c) Irritation test on the rabbit eye. Unp ublished repor t from Roure Incorporat ed, 3 January. Report number 2 179. Research Institute for Frag rance Mat erials, Inc. (I 978d) Capacity for allergic sensitization determined by the intrader mal test with Freund's Comple te Adjuva nt (FCAT) on guinea pigs. Unpu blished report from Ro ure Incorp orated, 25 Jan uar y. Report number 2176. Resea rch Institut e for F ragrance Ma terials, Inc. ( l978e) Determinat ion of phototoxicity in guinea pigs. Unp ublished report from Rou re Incorp ora ted, 25 January. Report numbe r 2 177. Research Institute for Fragrance Materials, Inc. (1985) Repor t on human maximization studies. RIFM repor t number 1919, Janu ary 7.
SI13
HEPTYL METHACRYLATE Synony m : Methacrylic acid, hept yl ester. CAS Registr y Number: 5459-37-0 CAS Registr y Name: 2-Pro penoic acid, 2-methyl-, hept yl ester Structure:
~
~H2
CH3-- (CH2) 6-- O-C-C-CH3
Nat ural occurrence: Ha s appa rently not been reported to occur in nature. Volume of use: The worldwide volume of use (1996) as a fragr an ce ingredient is less than I metric ton .
Biological data Acute tox icity Oral studies: Th e o ral LD so in SPF- albin o, Fullinsdorf mice was repo rted to be grea ter than 8 g/kg based on no deaths in 10 animals tested a t that dose after 10 days. Clinical signs of hypom otilit y a nd respiratory depression were observed only du ring the first 3 da ys after treatm ent (RIF M, 1978a). Int raperitoneal studies: Th e LD so by the ip route in SPF-a lbino, Fullinsdorf mice was reported to be greater than 4 g/kg based on 0/10 death s at that dose but less than 8 g/kg based on 10/10 deaths at that dose after 10 days. Clinical signs includ ed ataxia and respiratory depr ession ; death was caused by respirat ory insufficiency by the second da y afte r treatm ent (RIFM, 1978a). Based on these high do ses, no further acute to xicity studies were con sidered appro priate. Skin irritation Human st udies: No irrita tion was observed after a 48-hr closed patch test with 2% in petrolatum on the backs of2 5 health y, male and female volunteers (RIF M, 1985). Animal studies: In a n open epicutan eous test (Kleca k et al.. 1977) on guinea pigs, 3% hept yl methacr ylate in ethan ol was the highest non-irr itat ing concentration after single and repeated applications over 21 da ys; 10% and 30% in ethanol and the neat liquid all produced irrit at ion after a single application ; slight irritation was produced after repe ated applications with 10%; moderate to strong irritation was produced after repeated applications with 30% and the neat liquid (RIFM, 1978b). Mu cous membrane (eye) irritation Animal studies: A rabbit eye test was conducted in three ra bbits with undiluted heptyl meth acrylate. A O.I-ml aliq uot of the neat liquid was applied to the surface of one eye of each rabbit. The untreated eye of each rabbit served as a cont rol. Observat ion s were made immediately after instillation, and a t 1, 24, 48 a nd 72 hr and aga in a t 7 and 14 days. Sco res were recorded accord ing to the Draize scale for scoring ocular lesion s. Some red vessels in the conj unctiva of the eye of one rabbit was observed a t 24 and 48 hr, which clear ed by 72 hr. No altera tion of the co rnea was o bserved macroscopically (RIFM, 1978c). No irritation was observed in rabbi ts (three/dos e) after a O. l-ml aliquo t of either a 10% or 30% solut ion of heptyl metha crylate in dieth yl phthalate was applied to the surface of one eye of each rabbi t. The untreated eye of each rabbit served as a control. Scores were record ed acco rding to the Draize scale for scoring ocular lesion s. Observations were made of the eyes immediately after instillat ion , and at I, 24, 48, 72 hr and aga in at 7 and 14 days (RIFM, 1978c). Skin sensitization Human stu dies: A ma ximizat ion test (Kligma n, 1966; Kligman a nd Epstein, 1975) was carried out with 2% in petrolatum on 25 health y, male a nd female volunteers. Th e test concentration of 2% was based o n a repor ted maximum use concentra tion of 0.2% in con sumer produ cts. Application was under occlusion to the same site on the forea rms of all subjects for five altern ate-day 48-hr period s. Patch sites were pretrea ted for 24 hr with 5% aqueous sodium lau ryl sulfate (SLS) under occlusion for the initial pat ch only. Following a 1014-day rest period challenge pat ches were applied to fresh sites for 48 hr. Challenge appli cat ion s were preceded by 30-min applications of 7.5% aqueous SLS under occlusion on the left side whereas the test material
c. S. Letizia et 01.
SI14
was applied without SLS treatment on the right side. A fifth site challenged with petr olatum served as a control. No react ions were observed that were considered significa ntly irritant or allergic (RIF M, 1985). Animal studies: Six guinea pigs were tested in an open epicuta neous test (Klecak et al., 1977). A to tal of 21 daily induction applications at co ncentrations of 3%, 10% and 30% in ethanol and the neat liquid were followed 14 days later by an open challenge application with the non-irritating concentrat ion of 3% heptyl methacrylate in ethanol. There were no reactions to challenge in any of the experimental groups and it was conclud ed that heptyl methacrylate does not sensitize the guinea pig in this test procedure (R IFM, 1978b). Gu inea pigs (eight/dose) were tested in a Freund's compl ete adjuvant (FCA) test (Klecak et al., 1977) with induction via five intradermal injectio ns of a O.I-ml aliquot of a 5% emulsion of hept yl meth acrylate in FCA on days 0, 2, 4, 7 and 9. Induction was followed on days 21 and 35 with a topical cha llenge using the nonirritating concentration s of I% and 3% . Positive sensitization reactions were observed with 3% heptyl meth acr ylat e in 4/8 guinea pigs at 21 days and in 8/8 at 35 days; 1% hept yl meth acrylat e produced no sensitizat ion reactions (0/8) at 21 days and 1/8 reaction s at 35 days. It was concluded that heptyl methacrylate was a moderat e sensitizer for the guinea pig in the FCA test (RIFM, 1978d). Photo tox icity Anim al studies: No phototoxic properties were observed with heptyl methacrylate (concentration not specified) when applied to the skin of four albino guinea pigs per group for a 48-hr patch test. 4 hr after removal of the pat ch , the skin was irradiate d with either UVA (320-400 nm) for 30 min (Westinghouse FS 40 Black Lamp ) or with UVB (280-3 70 nm) irra dia tion for 15 min (Westingho use FS 40 Sunlamp ) (RIF M, 1978e).
Status Canadian Domestic Subst ances List European Inventory of Existing Commercial Chemical Sub stances Indicative Non-Exhaustive List TSCA Inventory List
Registered Registered 226-727-5 Listed Registered
References Klecak G ., Geleick H . and Frey J .R . (1977) Screening of fragr ance mat erials for allergenicity in the guinea pig. I. Comparison of four testing methods. Journal of the Society of Cosmetic Chemists 28, 53-64. Kligman A.M. (1966) The identification of co ntact allergens by hu man assay. III. The maximization test. A procedur e for screening and ra ting contact sensitizers. Journal of Investigative Dermat ology 47, 39J-409 .[Submitte d only for the methodo logy] Kligman A.M . and Epstein W. (1975) Updating the maximization test for identifying contact allergens. COil tact Dermatitis 1, 231- 239.[Submitted only for the meth od ology] Resear ch Institute for Fr agrance Materials, Inc. (l978a) Acut e toxicity studie s. Un published report from Roure Incorporat ed, 16 May. Report numb er 2180. Resear ch Institut e for Fragran ce Materi als, Inc. (1978b) Skin irritation and capac ity of allergenic sensitizat ion determined by the o pen epicutaneous test (OET) o n guinea pigs. Unpublished report from Roure Incorp orat ed, 25 Jan uary. Report numb er 2 178. Research Institute for Fragrance Ma terials , Inc. (l978c) Irritation test on the rabbit eye. Unp ublished repor t from Roure Incorporat ed, 3 January. Report number 2 179. Research Institute for Frag rance Mat erials, Inc. (I 978d) Capacity for allergic sensitization determined by the intrader mal test with Freund's Comple te Adjuva nt (FCAT) on guinea pigs. Unpu blished report from Ro ure Incorp orated, 25 Jan uar y. Report number 2176. Resea rch Institut e for F ragrance Ma terials, Inc. ( l978e) Determinat ion of phototoxicity in guinea pigs. Unp ublished report from Rou re Incorp ora ted, 25 January. Report numbe r 2 177. Research Institute for Fragrance Materials, Inc. (1985) Repor t on human maximization studies. RIFM repor t number 1919, Janu ary 7.