Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
experimental study
Adequacy of study:
key study
Study period:
≥ 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 422) but study period and year of publication not clear (≥ 1997) and only summary available in English.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): o-sec-butylphenol
- Substance type: Mono-alkylphenol
- Analytical purity: 99.15%

Test animals

Species:
rat
Strain:
other: Crj:CD(IGS)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
Males, 42 days
Females, from 14 days prior to mating to day 3 of lactation
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 12, 60, 300 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
13
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:


DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes


FOOD CONSUMPTION: Yes


HAEMATOLOGY: Yes


CLINICAL CHEMISTRY: Yes









Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
Reproductive performance and development of pups studies

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY: no animals died in any group. Salivation after dosing, decrease in activity and incomplete eyelid opening were observed in males and females of the 300 mg/kg group. In addition an ataxic gait was observed in females of the same group. In the 60 mg/kg group, decrease in locomotor activity was observed in a few males early in the administration period.


BODY WEIGHT AND WEIGHT GAIN: no adverse effects were detected in males and females of the 300 mg/kg group.


FOOD CONSUMPTION: no adverse effects were detected in males and females of the 300 mg/kg group.


HAEMATOLOGY: hematological examination of males revealed no adverse effects.


CLINICAL CHEMISTRY: Concentration of total cholesterol was also increased in males given 300 mg/kg.



ORGAN WEIGHTS: an increase in relative liver weight was observed in males and females


GROSS PATHOLOGY


HISTOPATHOLOGY: NON-NEOPLASTIC: hypertrophy of the centrilobular hepatocytes in males of the 300 mg/kg group.


HISTOPATHOLOGY: NEOPLASTIC (if applicable)


HISTORICAL CONTROL DATA (if applicable)


OTHER FINDINGS

Effect levels

open allclose all
Dose descriptor:
NOEL
Remarks:
repeated dose toxicity
Effect level:
12 mg/kg bw/day (actual dose received)
Sex:
male
Basis for effect level:
behaviour (functional findings)
Dose descriptor:
NOEL
Remarks:
repeated dose toxicity
Effect level:
60 mg/kg bw/day (actual dose received)
Sex:
female
Basis for effect level:
behaviour (functional findings)
Dose descriptor:
NOEL
Remarks:
reproductive and developmental toxicity
Effect level:
300 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: absence of reproductive toxicity

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Repeated dose toxicity

No animals died in any groups. Salivation after dosing, decrease in activity (decreased locomotor activity, adoption of a prone or lateral position, leaning) and incomplete eyelid opening were observed in males and females of the 300 mg/kg group. In addition, ataxic gait was observed in females of the same group. An increase in relative liver weight was observed in males and females of the 300 mg/kg group. On histopathological examination of the liver, hypertrophy of the centrilobular hepatocytes was observed in males of the 300 mg/kg group, whereas this change was not observed in females of the same group. The total cholesterol concentration was increased in the males of the 300 mg/kg group. No adverse effects were detected in terms of food consumption and body weight change in males and females of the 300 mg/kg group. The hematological examination of males revealed no adverse effects of o-sec-butylphenol. In the 60 mg/kg group, decrease in locomotor activity was observed in few males in the early administration period, but not in females. No adverse effects of o-sec-butylphenol at the dose level of 12 mg/kg were found.

The no observed effect dose levels (NOELs) for repeat dose toxicity are considered to be 12 mg/kg/day in males and 60 mg/kg/day in females.

Reproductive and developmental toxicity

No adverse effects were observed on copulation, fertility, maintenance of pregnancy, delivery, and lactation. In addition, o-sec-butylphenol did not affect the viability of neonates, sex ratio, body weight changes, and morphological appearance of pups.

The NOEL for reproductive and developmental toxicity is considered to be 300 mg/kg/day in males, females and offspring.

Applicant's summary and conclusion

Conclusions:
Regarding reepated dose toxicity, no adverse effects of o-sec-butylphenol at the dose level of 12 mg/kg in males and 60 mg/kg/day in females were found. Regarding reproductive and developmental toxicity, no adverse effects were observed on copulation, fertility, maintenance of pregnancy, delivery, and lactation. In addition, o-sec-butylphenol did not affect the viability of neonates, sex ratio, body weight changes, and morphological appearance of pups.
Executive summary:

An OECD 422 combined repeat dose and reproductive/developmental toxicity screening test was performed in rats for o-sec-butylphenol ( Japan Existing Chemical Data Base: study report period not clear, only abstract available in English). With regard to repeat dose toxicity, no animals died in any groups. Salivation after dosing, decrease in activity and incomplete eyelid opening were observed in males and females of the 300 mg/kg group. In addition, an ataxic gait was observed in females of the same group. An increase in relative liver weight was observed in males and females, and hypertrophy of the centrilobular hepatocytes in males of the 300 mg/kg group. Concentration of total cholesterol was also increased in males given 300 mg/kg. No adverse effects were detected on food consumption and body weight change in males and females of the 300 mg/kg group. In the 60 mg/kg group, decrease in locomotor activity was observed in a few males early in the administration period. The NOELs for repeat dose toxicity are considered to be 12 mg/kg/day in males and 60 mg/kg/day in females.

Regarding reproductive and developmental toxicity, no adverse effects were observed on copulation, fertility, maintenance of pregnancy, delivery, and lactation. In addition, o-sec-butylphenol did not affect the viability of neonates, sex ratio, body weight changes, and morphological appearance of pups. NOELs for reproductive and developmental toxicity are considered to be 300 mg/kg/day in males, females and pups.