IJT - CIR - February 2024 - 99S

Fiume et al.
99S
Table 2. (continued)
Test Substance
Caprylyl Alcohol (1octanol)
Summary
Data
single dose (acute) toxicity-dermal: 2-4 g/kg in rabbits with 24-h occlusive patches of 1, 2, and 4 g/kg; >5 g/kg in NZW
rabbits; >.5 g/animal in guinea pigs
single dose (acute) toxicity-oral: >5 g/kg in male and female Wistar rats; 18.24 g/kg in male and female Holtzman albino
rats
reproductive and developmental toxicity: in Wistar rats dosed by gavage with 130-1300 mg/kg bw/day on days 6-15 of
gestation, the LOAEL was 130 mg/kg bw/day for maternal toxicity and the NOAEL was 1300 mg/kg bw/day for
teratogenicity and fetotoxicity; in 15 female Sprague-Dawley rats dosed 7 h/day on days 1-19 of gestation by whole
body exposure to 400 mg/m3, the NOAEC was >400 mg/m3 for maternal toxicity, fetotoxicity, and teratogenicity
genotoxicity: not mutagenic in an Ames test (≤5000 µg/plate) with and without metabolic activation
carcinogenicity: no carcinogenicity was seen in male and female mice injected intraperitoneally 3x/wkwith ≤500 mg/kg bw
for 8 wks and observed for a further 16 weeks
dermal irritation - non-human: slightly irritating when applied undiluted to 3 female NZW rabbits using 4-h semiocclusive
patches
dermal irritation and sensitization - human: non-irritating; 2%in petrolatum was not a sensitizer in a maximization study in
25 subjects
Decyl Alcohol
ocular irritation: irritating to the eyes of NZW rabbits (n=3) when instilled undiluted
single dose (acute) toxicity-dermal: LD50 in rabbits, 3.5 mL/kg
single dose (acute) toxicity-oral: LD50 in rats, 9800 mg/kg
single dose (acute) toxicity-inhalation: no deaths with exposure to concentrated vapors for 8 h
irritation - human: produced no irritation in a 48 h closed-patch test in 25 human subjects when tested at 3% in
petrolatum
Ethylhexyl Alcohol
absorption, distribution, metabolism, and excretion: in vitro dermal absorption rates were .22 mg/cm2/h for rats and .038
mg/cm2/h for humans, indicating the rate of absorption in humans was 5.78 times slower than in the rate in the rat;
efficiently absorbed following oral administration to rats, rapidly excreted in respiratory CO2 (6-7%), feces (8-9%) and
urine (80-82%), with essentially complete elimination by 28 h after administration, only 3% was excreted unchanged,
and the major metabolite, 2-ethylhexanoic acid, appeared in the urine; in perfused livers of female Sprague-Dawley rats,
2-ethylhexyl alcohol inhibited mitochondrial beta-oxidation of fatty acids in-vitro and in-vivo, resulting in decreased
levels of plasma ketones, and increased levels of hepatic total lipids and triglycerides, but peroxisomal oxidation
pathways were not inhibited
single-dose (acute) toxicity-dermal: in several studies, LD50 values ranged from 1980- 5000 mg/kg bw; LD50 >3000 mg/kg
in rats; LD50 of 1980-2600 mg/kg in rabbits
single dose (acute) toxicity-oral: numerous LD50 values have be reported for several species; mice: 2500-4460 mg/kg; rats:
2047-7000 mg/kg; guinea pigs: 600-2820 mg/kg; rabbits: 1180-1470 mg/kg
single dose (acute) toxicity-inhalation: LC50 (4 h) in rats was >.89 mg/L but <5.3 mg/L; LC50 > 227 ppm (6 h) in mice and
guinea pigs
repeated dose toxicity-dermal: groups of 10 rats/sex were dosed dermally with 0, 500, or 1000 mg/kg bw/day (5 days
occlusive, 2 days untreated, 4 days treated); females of the 500 and 1000 mg/kg groups exhibited minimal exfoliation,
decreased spleen weight and increased serum triglycerides
repeated dose toxicity-oral: NOEL of 125 mg/kg bw/day and estimated NOAEL of 250 mg/kg bw/day in a 90-day gavage
study in both mice and rats dosed with 0-500 mg/kg bw/day
repeated dose toxicity-inhalation: NOAEC was 120 ppm (ie, 638.4 mg/m³) in male and female Wistar rats in a 90-day
whole-body exposure study with exposure to 0-120 ppm 6h/day, 5 days/wk
reproductive and developmental toxicity: exposure of female rats for 7 h per day to 850 mg/m3 on gestation days 1-19
reduced maternal feed intake, but did not produce any malformations
estrogenic activity: in an E-SCREEN assay using T47D human breast cancer cells, weak estrogenic activity was observed
(additional details were not provided)
genotoxicity: in vitro, negative in numerous Ames assays, a liquid suspension assay, mouse lymphoma assay, and
unscheduled DNA synthesis assay; in a 3H-thymidine assay, there was a dose-dependent inhibition of 3H-thymidine
into replicating DNA, with a dose-dependent increase in the ratio of thymidine incorporated into acid-soluble DNA;
the urine of rats dosed orally with 1000 mg/kg bw was not mutagenic; in vivo, not genotoxic in a mouse micronucleus
test or a transformation assay
carcinogenicity: in B6C3F1 mice (50/sex/group) dosed 5 days/wk with 0, 50, 200, or 750 mg/kg bw/day by gavage for 18
mos, an adverse trend in increased liver carcinoma observed in females of the 750 mg dose group was attributed to
toxicity at this dose, body wt gain decreased and mortality increased, and mortality was 52% in females of the 750 mg/kg
dose group; in a 24-mos study, F344 rats (50/sex/group) were dosed 5 days/wkwith 0, 50, 150, or 500 mg/kg bw/day by
gavage, and animals dosed with ≥150 mg had decreased body weight gains, lethargy and unkemptness
dermal irritation - non-human: 4-h occlusive patches of undiluted test material were irritating to rabbit skin (n= 3 males);
application of .5 mL under occlusion on intact rabbit skin for 1, 2, 4, and 24 hours resulted in high irritation, and the
effects seen after 7 days were not reversible
clinical irritation and sensitization - human: in a 48-h occlusive patch test in 29 male volunteers, 4% in petrolatum was not
irritating; not a sensitizer in a maximization study
ocular irritation: instillation of 20 µg into the conjunctival sac of rabbit eyes caused moderately severe irritation of the
cornea
(continued)
4,6
4
Reference
5,64

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