2-sec-butylphenol

Endpoint summary

Description of key information

NOEL (repeated dose toxicity): 12 mg/kg bw/day (actual dose received) (male)
NOEL (repeated dose toxicity): 60 mg/kg bw/day (actual dose received) (female)
NOEL (reproductive and developmental toxicity): 300 mg/kg bw/day (actual dose received) (male/female)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: Crj:CD(IGS)

Sex:

male/female

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

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

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

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

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

Critical effects observed:

not specified

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

12 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Acceptable

Organ:

liver

Additional information

Repeated dose toxicity oral:

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.

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.

Justification for classification or non-classification

Findings in the combined repeated dose toxicity study are not sufficient for classification according to CLP 1907/2006 regulation.