Registration Dossier

Administrative data

Description of key information

LD50 oral, Swiss inbred white mice tested by intragastic administration, 10 mice per dose, doses of 350, 400, 550, 600, 650, 700, and 800 mg/kg bw: 568 mg/kg bw (Federal Institute for Occupational Safety and Health, Division for Chemicals and Biocides Regulation, Germany (2009); Shell Development Company (1950))

LD50 dermal, New Zealand White rabbits, percutaneous administration, single dose, 30% PTBBA solution in DMSO (w/v): > 900 mg/kg bw;
LD50 dermal: The acute single dose percutaneous LD50 value of PTBBA (no data on purity) as a 30% solution in DMSO (w/v) was found to be approximately 300 mg/kg in Carworth Farm E strain (CFE) rats in a study using 2 males and 2 females each at dose levels of 75, 150, 300, and 900 mg/kg bw. (Federal Institute for Occupational Safety and Health, Division for Chemicals and Biocides Regulation, Germany (2009)), Shell Research Ltd. London (1975))
LC50 inhalation, groups of 6 male and 6 female Fischer rats exposed to PTBBA dust at doses of 0.0, 0.495 , 0.668, 0.958 or 1.802 mg/l for 4 hours (MMAD in the range of 4.0-5.5 micrometer: > 1.802 mg/kg. (Federal Institute for Occupational Safety and Health, Division for Chemicals and Biocides Regulation, Germany (2009), Darmer et al. (1982, 1984), Lu et al. (1987))

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: data contained in EU risk assessment report of the substance - credibility is assumed. Reference to origin (Shell Development Company)
Reference:
Composition 0
Composition 0
Principles of method if other than guideline:
Determination of oral LD 50 of the test substance by intragastical administration of different concentrations in an aqueous suspension of gum acacia.
GLP compliance:
not specified
Test material information:
Composition 1
Species:
mouse
Strain:
other: Swiss inbred
Sex:
not specified
Details on test animals and environmental conditions:
white mice
Route of administration:
other: intragastic
Vehicle:
other: gum acacia in water
Details on oral exposure:
administration of an aqueous suspension of the test substance in gum acacia
Doses:
350, 400, 550, 600, 650, 700, and 800 mg/kg bw
No. of animals per sex per dose:
10
Dose descriptor:
LD50
Effect level:
568 mg/kg bw

Doses of 350, 400, 550, 600, 650, 700, and 800 mg/kg bw were given to 10 mice each resulting in the following mortalities: after administration of 350 mg/kg 1/10 mice died on day 2; after administration of 400 mg/kg 4/10, after 550, 600, and 650 mg/kg 5/10 each, after 700 mg/kg 7/10, and after 800 mg/kg all mice died within 24 hours. The mice were mildly depressed within 1/3 hours after dosing. Within an hour, signs of muscular distress, marked incoordination and the Straub tail effect (spinal cord excitant) were present. At 5 hours a paralysis of the forelegs was evident in two thirds of the mice. In 3 of these, response of the tail and paws to painful stimuli was depressed or absent, but recovery occasionally followed even this deep depression. The pathologic changes noted in the 22 mice autopsied included signs off lung irritation, hemorrhage of the lungs, increased pigmentation of the liver, denuding of the epithelium of the intestines, and hyperemia of the intestines.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
568 mg/kg bw
Quality of whole database:
reliable reference

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: data contained in EU risk assessment report of the substance - credibility is assumed. (In the EU report it is referred to the original study of Darmer et al.(1982, 1984) and Lu et al. (1987))
Reference:
Composition 0
Composition 0
Composition 0
Composition 0
Principles of method if other than guideline:
Exposition of rats to dust of PTBBA. Determination of acute inhalation toxicity (LC50).
GLP compliance:
not specified
Test material information:
Composition 1
Species:
rat
Strain:
other: Fischer
Sex:
male/female
Route of administration:
inhalation: dust
Type of inhalation exposure:
not specified
Vehicle:
not specified
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.802 mg/L air

At the highest concentration of 1.802 mg/l 2/6 males and 1/6 females died. This indicates that the LC50 is > 1.802 mg dust/l. However, other major toxicological effects were seen at all concentrations tested and a No-Effect-Level for a single four hour exposure could not be determined. At the lowest concentration of 0.495 mg/l effects on testes, in spinal cord and on rate of body weight gain were noted. Testicular effects were characterised among others by decreased sperm counts and microscopic lesions including reduction of tubular multinucleated cells. The forelimb neuropathy was described microscopically as multifocal poliomyelopathy. Decreased rate of body weight gain was observed in both sexes on days 4 and 14 exposed to all dose levels of PTBBA

Conclusions:
According to the cited results the test substance provided as dust to male and female rats has a LC50 at greater than 1.802 mg dust/L.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
1.8 mg/m³
Quality of whole database:
reliable reference

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: data contained in EU risk assessment report of the substance - credibility is assumed. Reference to origin (Shell Research Ltd. London)
Reference:
Composition 0
Composition 0
Principles of method if other than guideline:
Dermal acute toxicity (LD50) of the test substance determined using rats and rabbits, application percutaneous in DMSO solution or as dry powder
GLP compliance:
not specified
Test material information:
Composition 1

The acute single dose percutaneous LD50 value of PTBBA (no data on purity) as a 30% solution in DMSO (w/v) was found to be approximately 300 mg/kg in Carworth Farm E strain (CFE) rats in a study using 2 males and 2 females each at dose levels of 75, 150, 300, and 900 mg/kg bw. After application of 75 mg/kg none of the rats died, after application of 150 mg/kg 0/2 males and 1/2 females died on day 2, after application of 300 mg/kg 2/2 males and 0/2 females died within 4 days, after application of 900 mg/kg all rats died within 4 days. No further information is given (Shell Research Ltd. London, unpublished report 1975).

In studies with New Zealand White rabbits, however, a dermal LD50 value of > 900 mg/kg bw for a 30% solution in DMSO (w/v), and of > 2000 mg/kg bw for the dry powder were determined. The acute single dose percutaneous LD50 value of 4-tert- butylbenzoic acid (no data on purity) as a 30% w/v solution in DMSO was found to be greater than 900 mg/kg, the maximum volume of the most concentrated solution that could be used. The LD50 value of the dry powder was found to be greater than 2000 mg/kg in rabbits. No pathological lesions were found in the tissues of the rabbits exposed to the powdered substance. No further information is given (Shell Research Ltd. London, unpublished report 1975).

Conclusions:
According to the cited results the LD50 (percutaneous) of the test substance has been determined to be approximately 300 mg/kg in male and female Carworth Farm E strain (CFE) rats.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
300 mg/kg bw
Quality of whole database:
reliable reference

Additional information

EU risk assessment report of 2009, p.52: 4.1.2.2.3 Summary of acute toxicity, 4.1.2.3 Human data on acute toxicity of 4 -tert-butylbenzoic acid are not available. In studies with rats, oral LD50 values of > 550 mg/kg and < 800 mg/kg bw were detected with females being slightly more sensitive than males (Hunter et al., 1965; Procter & Gamble Comp. 1986; Shell Comp. 1950). Testicular atrophy was produced in male rats exposed to a single dose of 500 mg/kg, and degeneration of the generative cells in the seminiferous tubules was observed. The ovaries of surviving female rats were of normal appearance and presented no histological evidence of abnormal oogenesis (Hunter et al., 1965). The oral LD50 for mice was determined at 568 mg/kg bw (Shell Comp. 1950). An inhalation LC50 was not determined but exposure of rats to 1.802 mg dust/l/4 hours resulted in death in 2/6 male and 1/6 female rats. This indicates an LC 50 of > 1.8 mg/l. In these experiments testicular and CNS changes and changes in body weight were noted at the lowest concentration tested at 0.495 mg/l (Darmer et al., 1982; Darmer et al., 1984; Lu et al., 1987). The assessment of acute dermal toxicity is difficult, because the available data demonstrated great species differences (Shell Research Ltd. London, unpublished report 1975). In rats, a dermal LD50 of approximately 300 mg/kg resulted when a 30% substance solution in DMSO was tested. In rabbits the dermal LD50 was found to be > 2000 mg/kg when the dry powder was applied.


Justification for selection of acute toxicity – oral endpoint
Basis for the classification and labelling of the Risk Assessment Committee (ECHA/RAC/CLH-O-0000001579-64-01/A1, Adopted 21 February 2011) as acute tox. 4- H302.

Justification for selection of acute toxicity – inhalation endpoint
Summary of data cited in reliable reference (European Union Risk Assessment Report - 4-TERT-BUTYLBENZOIC ACID- RISK ASSESSMENT
July 2009, FINAL APPROVED VERSION)

Justification for selection of acute toxicity – dermal endpoint
Summary of data cited in reliable reference (European Union Risk Assessment Report - 4-TERT-BUTYLBENZOIC ACID- RISK ASSESSMENT
July 2009, FINAL APPROVED VERSION)

Justification for classification or non-classification

EU risk assessment report of 2009, p.52:

Based on the above data, 4-tert-butylbenzoic acid is to be classified "Xn, harmful" and labelled with "R 22, Harmful if swallowed". The TC C&L in September 2007 agreed that for acute toxicity the available LC50 for inhalation and the LD50 for dermal application were not sufficient for classification. Committee for Risk Assessment RAC Adopted 21 February 2011, p. 5: Based on the data above, the test substance 4 -tert-butylbenzoic acid has been classified according to EC No. 1272/2008 as "Acute Tox. 4 - H302 - Harmful if swallowed.