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Administrative data

Description of key information

The NOAEL for oral repeated dose toxicity was 150 mg/kg bw after oral administration (gavage) in an OECD 406 study, based on the structural analogue CAS 10042-59-8.

To substantiate this read-across, an OECD guideline 422 Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test will be performed in the first half of 2021 with alcohols C13 -15 branched and linear.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See justification attached to IUCLID chapter 13.
Reason / purpose:
read-across source
Key result
Dose descriptor:
NOAEL
Effect level:
150 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
body weight and weight gain
food consumption and compound intake
food efficiency
other: based on human relevant hazards (effects due to peroxisomal proliferation: increased mean absolute and relative liver weights, diffuse hypertrophy of the liver cells, thyroid gland and pituitary gland were excluded)
Remarks on result:
other: as determined from read-across CAS 10042-59-8
Critical effects observed:
yes
Lowest effective dose / conc.:
150 mg/kg bw/day (nominal)
System:
hepatobiliary
Organ:
liver
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
no
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
600 mg/kg bw/day (nominal)
System:
other: reduced body weight
Organ:
other: general toxicity
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
yes
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
150 mg/kg bw/day
Study duration:
subchronic
Species:
rat
System:
other: general toxicity: reduced b.w. and food consumption

Additional information

A repeated dose toxicity test was performed with the structural analogue CAS 10042-59-8. The study was conducted according to OECD guideline 408 and fulfilled GLP criteria. Groups of 10 male and 10 female Fischer 344 rats received dose levels of 30, 150 or 600 mg/kg bw test substance per gavage for three months. Animals were observed for clinical signs at least daily. Gross and microscopic examinations were performed on all animals from all dosage groups. Also, clinical chemistry, hematology, urinalysis or ophthalmoscopic examinations were conducted and organ weights were taken. Substance-related effects were seen at 600 mg/kg in both sexes and at 150 mg/kg in females, only. No substance-related deaths occurred at 600 mg/kg bw. All males and females showed salivation one hour after administration and urine-smeared fur in the anogenital region was recorded for males and females for 3 to 4 hours after administration. At 600 mg/kg bw/day, reduced food consumption was recorded in animals of both sexes as well as impaired body weight gain including reduced body weights at the end of administration in males. Ophthalmoscopy revealed no treatment-related changes.

At 600 mg/kg bw/day, hematology showed a decrease in platelets. The toxicological relevance of this singular finding is unclear. Globulins and cholesterol were decreased in both sexes and triglycerides only in males, while albumin was increased. These changes might be indicative of increased liver metabolism. There was also an increase in cyanide- insensitive palmitoyl-CoA-oxidation in both sexes, which is typical for peroxisome proliferation. Correspondlingly, pathology showed an increased absolute and relative liver weight in both sexes, which was associated with diffuse hepatic hypertrophy. There was also a loss of fatty infiltration of liver cells in males only. Diffuse follicular hypertrophy in the thyroid gland in males and vacuolation of basophilic (thyrotrophic) cells in the glandular part of the pituitary gland in males are also secondary to peroxisome proliferation and parallelly induced xenobiotic metabolism, which results in an increased elimination of T3/T4 from rat serum by increased glucuronidation. At 150 mg/kg bw/day, one female showed diffuse hepatic hypertrophy, resulting in an increase in relative liver weight in one female only. Thus, the NOAEL was 150 mg/kg bw/day in males and 30 mg/kg bw/day in females mainly based on liver effects indicative for peroxisomal proliferation. Peroxisomal proliferation is a rodent-specific effect and not relevant for human hazard. Therefore the NOAEL relevant for human hazard is 150 mg/kg bw based on body weight effects.

To substantiate this read-across, an OECD guideline 422 Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test will be performed in the first half of 2021 with alcohols C13 -15 branched and linear.

Justification for classification or non-classification

Based on the available information the substance does not need to be classified for oral repeated dose toxicity, as in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.