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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: data is contained in EU risk assessment report of the substance - credibility is assumed. Reference to origin (HRC (1994, 1995))

Data source

Referenceopen allclose all

Reference Type:
other: EU risk assessment report
Title:
No information
Author:
Federal Institute for Occupational Safety and Health, Division for Chemicals and Biocides Regulation, Germany
Year:
2009
Bibliographic source:
European Union Risk Assessment Report, 4-tert-butylbenzoic acid, CAS No: 98-73-7, EINECS No: 202-696-3, p. 54, Final Approved Version, July 2009
Reference Type:
study report
Title:
Unnamed
Year:
1994
Reference Type:
study report
Title:
Unnamed
Year:
1995

Materials and methods

Principles of method if other than guideline:
5-day and 28-d repeated dose inhalation toxicity study using rats (male/female), snout-only exposition to test substance, subsequent examination of substance-induced effects
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: particulate aerosol generated from micronised test substance powder (MMAD 4.1-4.4 µm, ≥ 65 % MMAD < 7 µm).

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
other: snout-only
Vehicle:
air

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

There were no clinical signs, bodyweight changes, effects on food and water consumption, macroscopic pathology findings or differences in organ weights that were considered to be attributable to exposure to PTBBA. Samples of a number of organs were preserved, but not prepared for microscopic pathology (HRC, 1994).

Liver weights of high dose females were significantly higher than control values (+9%). There were no other clinical signs, bodyweight changes, effects on food consumption, macroscopic or microscopic changes in main study rats that were attributable to p-tert butyl benzoic acid. Behavioural observations revealed a slight increase in the incidence of body tremor in the low and high dose group males after 1 week of exposure. After 4 weeks the incidence of body tremor was increased for high dose males. Among high dose males, there was a significant decrease in activity counts with tendency towards decreased rearing counts. Also, facial staining and hair loss occurred with slightly increased frequency in high dose males. The number of males with decreased arousal and urinating/defecating while in the arena was increased in the mid and high dose groups. No similar findings were noted among treated females. Neither the microscopic examination of the organs examined in the main study nor the examination of the nervous tissues in satellite rats revealed any lesions, which were attributable to 4-tert-butylbenzoic acid. The occurrence of body tremor might be considered as the most sensitive and earliest neurobehavioural effect. Since no behavioural change was noted for low dose males after 4 weeks of exposure and no body tremor was observed for mid dose males, the NOAEC was considered to be 5 mg/m³ for male rats. The authors proposed a NOAEC of 15 mg/m³ for female rats. Based on the knowledge that the liver was a target organ in other repeated dose studies, the rapporteur’s opinion is that due to increased liver weight 5 mg/m³ should also be considered as the NOAEC for female rats. (HRC, 1995)

Applicant's summary and conclusion

Conclusions:
According to the results of this study the inhalation NOAEC for the test substance is 5 mg/m³.