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Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproductive Toxicity

READ ACROSS DATA: C16-C30 highly purified light mineral oil (60% paraffins, 40% naphthenes)

1-generation reproductive/developmental Test (OECD TG 415) - Dermal administration in females.

NOAEL for fertility, maternal toxicity and developmental toxicity >= 2000 mg/kg bw/day (highest dose tested)

READ ACROSS DATA: C16-C30 highly purified light mineral oil (60% paraffins, 40% naphthenes)

1-generation reproductive/developmental Test (OECD TG 415) - Dermal administration in males; 13-weeks prior to mating.

NOAEL for male fertility (sperm count, sperm morphology and spermatogenesis) for mineral oil >= 2000 mg/kg bw/day (highest dose tested)

READ ACROSS DATA: C13-C22 hydrocarbon fuel (30% n- & 70% iso-paraffins)

2-generation reproductive/developmental Test (OECD TG 416) - Oral administration in males and females.

NOAEL for fertility and developmental toxicity >= 750 mg/kg bw/day

SUPPORTING DATA:  JP-8 Fuel (C9-C16 Aliphatics, 25% aromatics)

1-Generation Reproduction Toxicity Study (OECD TG 415) - Male Fertility Test – Oral Administration - 90d prior to mating, the NOAEL >=3000 mg/kg/day, which was the highest dose tested.

Female fertility NOAEL >= 1500 mg/kg (highest dose tested). Developmental NOAEL = 750 mg/kg (decreased BW).

READ ACROSS DATA: C9-14 aliphatics (<2% aromatic)

 

Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test (OECD TG 422) – Oral Administration (decane) - The NOAEL for developmental toxicity was ≥1000 mg/kg/day and the NOAEL for reproductive toxicity was ≥1000 mg/kg/day.  

 

Reproduction / Developmental Toxicity Screening Test (OECD TG 422) - Oral Administration (undecane) - The NOAEL for developmental toxicity was ≥1000 mg/kg/day and the NOAEL for reproductive toxicity was ≥1000 mg/kg/day.

 

READ ACROSS DATA: C9-14 aliphatics (2-25% aromatic)

Reproduction / Developmental Toxicity Screening Test (OECD TG 421) - Inhalation Administration - The NOAEL for developmental toxicity was ≥300 ppm (1720 mg/m3).

Additional information

READ ACROSS DATA: C14-C20 aliphatics (<2% aromatic)

A reproductive/pre-natal developmental one-generational study was conducted to evaluate the reproductive performance (gonadal function, all 4 stages of the estrus cycle, fertilization, implantation of the egg, gestation period and parturition) of a C16-C30 highly purified light mineral oil (60% paraffins, 40% naphthenes). The pre-natal developmental phase also evaluated pup growth and development up to weaning. Female Sprague-Dawley rats were dermally exposed to test material for 10 weeks premating period (5 days/week), a 3-week mating period (5 days/week) and up to gestation day 20. Test material was applied once daily to clipped, intact dorsal skin at a dose level of 125, 500, 2000 mg/kg bw/day. No clinical signs of systemic toxicity were observed and there were no effects on maternal body weight and food consumption. No differences were observed in mean numbers of implantation sites, live pups/litter, live birth index (total pups born alive/total pups born) either at birth, or on days 4 or 21 postpartum. There was no change in mean pup body weights and no pathological observations were seen in necropsied organs of the pups. NOAEL for mineral oil was ≥ 2000 mg/kg bw/day for fertility and pre-natal development. In males exposed to the same test substance for 13 weeks prior to mating, the reproductive performance was evaluated with regard to fertility, sperm count, sperm morphology and spermatogenesis. No changes in male reproductive organ weights or performance were observed. NOAEL for fertility was ≥ 2000 mg/kg bw/day.

READ ACROSS DATA: C13-C22 aliphatics (<2% aromatic)

F0 and F1 male and female rats were administered an oral gavage dose (50, 200 or 750 mg/kg bw/day) of a C13-C22 hydrocarbon fuel comprised primarily of aliphatic constituents (30% n- and 70% iso-paraffins) 5 days/week for at least 70 days premating and 14 days mating (for males). Test substance had no effect on reproductive performance (fertility), gestation length and parturition in both F0 and F1 rats. There were no test-related effects on postnatal survival, mortality, systemic toxicity, anogenital distance and pup weights in F1 and F2 litters. , NOAEL for fertility was greater than 750 mg/kg bw for males and females.

SUPPORTING DATA: JP-8 Fuel (C9-C16 Aliphatics, 25% Aromatics) 

There were several studies located for the structurally analogous test material, JP-8 fuel. JP-8 fuel was examined for reproductive toxicity in a 70 day male and in a 90 day female one generation reproductive toxicity study (OECD TG 414). For the male reproductive toxicity study, the reproductive NOAEL 3000 mg/kg/day for male rats, which was the highest dose tested. For the female reproductive toxicity study, the reproductive NOAEL 1500 mg/kg/day for female rats, which was the highest dose tested. The F1 (fetus) NOAEL = 750 mg/kg/day based on a decrease in body weight that correlated to a decrease in maternal body weight.

READ ACROSS DATA: C9-14 aliphatics (<2% aromatic) 

 

C9-C14 aliphatic, <2% aromatic hydrocarbon fluids (decane) were examined for reproductive toxicity in a 28-day combined repeated dose toxicity study with the reproduction / developmental toxicity screening test (OECD TG 422).  C9-C14 aliphatic, < 2% aromatic hydrocarbon fluids were administered oral gavage at a dose of 0, 25, 150, or 1000 mg/kg/day to groups of Sprague-Dawley rats. It was concluded that C9-C14 aliphatic, <2% aromatic hydrocarbon fluids did not induce reproductive toxicity in the parental animals and no effects on the endocrine system were observed.  Therefore, the NOAEL was determined to be ≥1000 mg/kg bw/day. 

 

C9-C14 aliphatic, <2% aromatic hydrocarbon fluids (undecane) were examined in a reproduction / developmental toxicity screening test (OECD TG 422).  C9-C14 aliphatic, <2% aromatic hydrocarbon fluids were administered by oral gavage at a dose of 0 (vehicle), 100, 300, 1000 mg/kg/day to groups of Sprague-Dawley rats. It was concluded that C9-C14 aliphatic, <2% aromatic hydrocarbon fluids did not induce reproductive toxicity in the parental animals and no effects on the endocrine system were observed.  Therefore, the NOAEL was determined to be ≥1000 mg/kg bw/day. 

 

READ ACROSS DATA: C9-14 aliphatics (2-25% aromatic) 

 

C9-14 aliphatics (2-25% aromatic) hydrocarbon fluids were examined for reproductive toxicity in a reproduction / developmental toxicity screening test (OECD TG 421). C9-14 aliphatics (2-25% aromatic) hydrocarbon fluids were administered by inhalation at a dose of 0,100, and 300 ppm to groups of rats. It was concluded that C9-14 aliphatics (2-25% aromatic) hydrocarbon fluids did not induce reproductive toxicity in the offspring or in the parental animals. Therefore, the NOAEL was determined to be ≥300 ppm (1720 mg/m3).

Effects on developmental toxicity

Description of key information

One developmental study was available on C16-C20 n-alkanes, isoalkanes, cyclics, <2% aromatics showing a NOAEL>1000 mg/kg/day for both maternal and developmental toxicity.

READ ACROSS DATA: C16-C30 highly purified light mineral oil (60% paraffins, 40% naphthenes)

Pre-natal development toxicity (Similar to OECD TG 414) - Dermal, oral and inhalation exposure (gestation days 6-19). NOAEL for developmental toxicity was 2000 mg/kg bw/day (dermal), 1000 mg/m3 (inhalation) and 5000 mg/kg bw/day (oral gavage).

Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Additional information

One developmental study was available in rats orally exposed to C16-C20 n-alkanes, isoalkanes, cyclics, <2% aromatics showing a NOAEL>1000 mg/kg/day for both maternal and developmental toxicity.

READ ACROSS DATA: C16 to C30 highly purified light mineral oil (60% paraffins, 40% naphthenes)

A series of studies were conducted to evaluate the teratogenic effects of a C16-C30 light mineral oil in pregnant Sprague-Dawley rats by three separate routes of exposure; inhalation (1000 mg/m3), dermal (2000 mg/kg bw/day), oral gavage (5000 mg/kg bw/day) with exposures on gestation days 6-19. Due to low vapor pressure, the mineral oil was delivered as an aerosol for the inhalation study though aerosol particle size generated was well within the respirable range. There were no observable maternal effects (food consumption, body weight gain) irrespective of route of exposure. No adverse effects on reproductive parameters (implantation number, resorptions, fetal viability) or fetal parameters (body weight, crown-rump length) were observed in any of the studies. There was a clear lack of teratogenicity with regard to abnormal ossification, and adverse effects to external or soft tissue. Spontaneous anomalies were noted in some exposure groups but were not considered exposure related since incidence of such occurrences were similar in the sham-exposed groups. NOAEL for developmental toxicity was ≥ 2000 mg/kg bw/day (dermal), 1000 mg/m3 (inhalation) and 5000 mg/kg bw/day (oral gavage).

Justification for classification or non-classification

These findings do not warrant the classification of C14-C20 aliphatics, <2% aromatic hydrocarbons as teratogenic under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under the Directive 67/548/EEC for dangerous substances.