Butyl toluene-4-sulphonate

Endpoint summary

Description of key information

Acute Oral Toxicity

Under the conditions of the study the acute oral LD50 was determined to exceed 2000 mg/kg bw.

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

Study period:

17 September 2019 to 16 October 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines (Appendix to Director General Notification, No. 12-Nousan-8147)

Version / remarks:

November 2000

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Purity/Composition correction factor: No correction factor required.
- Specific gravity / density: 1.1188 (g/cm^3) at 20.8 °C (determined by the Test Facility)

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (approximately 8 - 9 weeks old)
- Weight at study initiation: 149 - 195 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3 - 4 hours after administration of the test material. Water was available.
- Housing: Animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages containing sterilised sawdust as bedding material equipped with water bottles. For psychological/environmental enrichment, animals were provided with paper, except when interrupted by study procedures/activities.
- Diet: Pelleted rodent diet, ad libitum
- Water: Municipal tap-water, ad libitum
- Acclimation period: At least 5 days before the commencement of dosing
- Condition: Outbred, SPF-Quality
- Method of randomisation in assigning animals to test and control groups: Animals were assigned to the study at the discretion of the co-ordinating biotechnician, with all animals within ± 20 % of the sex mean body weights. Animals in poor health or at extremes of body weight range were not assigned to the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 33 - 68 % (relative). Values that were outside the targeted range (of 40 to 70%) occurred for 3 days with a minimum of 33 % and were without a noticeable effect on the clinical condition of the animals or on the outcome of the study.
- Air changes: 10 or more air changes per hour with 100 % fresh air (no air recirculation)
- Photoperiod: A 12-hour light/12-hour dark cycle was maintained.

IN-LIFE DATES
- From: Not reported
- To: 16 October 2019

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE: Not applicable

DOSAGE PREPARATION: Not applicable. The test material was administered as received.

MAXIMUM DOSE VOLUME APPLIED: The dose volume for each animal was based on the body weight measurement prior to dosing. Dose volume (mL/kg body weight) was calculated as follows: Dose level (g/kg) / spec.gravity or density (g/mL) x purity correction factor.

CLASS METHOD
The toxicity of the test material was assessed by stepwise treatment of groups of 3 females. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg.
The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test material.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Two groups of 3 females were treated at a dose level of 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from their cage during observation, unless necessary for identification or confirmation of possible findings.
Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded and graded for severity (if appropriate).
Animals were weighed individually on Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: Yes. All animals were sacrificed by oxygen/carbon dioxide procedure at the end of the observation period and subjected to necropsy. All internal macroscopic abnormalities were recorded.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the study.

Clinical signs:

other: Hunched posture and piloerection were noted for all animals between Days 1 and 4. Uncoordinated movements were noted for three out of six animals on Day 1 and ptosis was noted for two animals on Day 1.

Gross pathology:

Macroscopic post mortem examination revealed abnormalities of the clitoral glands (tan foci) in two out of six animals. In one animal, the caecum was distended with gas. Macroscopic post mortem examination of the other animals at termination did not reveal any test material related abnormalities.

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of the study the acute oral LD50 was determined to exceed 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of the test material was investigated in a study which was conducted in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF 12-Nousan-8147, under GLP conditions, in line with the Acute Toxic Class Method.

During the study, the test material was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

Under the conditions of the study no mortality occurred. Hunched posture and piloerection were noted for all animals between Days 1 and 4. Uncoordinated movements were noted for three out of six animals on Day 1 and ptosis was noted for two animals on Day 1. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. Macroscopic post mortem examination revealed abnormalities of the clitoral glands (tan foci) in two out of six animals. In one animal, the caecum was distended with gas. Macroscopic post mortem examination of the other animals at termination did not reveal any test material related abnormalities.

The acute oral LD50 value in Wistar Han rats was determined to exceed 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute Oral Toxicity

The acute oral toxicity of the test material was investigated in a study which was conducted in accordance with the standardised guidelines OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100 and JMAFF 12-Nousan-8147, under GLP conditions, in line with the Acute Toxic Class Method. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, the test material was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

Under the conditions of the study no mortality occurred. Hunched posture and piloerection were noted for all animals between Days 1 and 4. Uncoordinated movements were noted for three out of six animals on Day 1 and ptosis was noted for two animals on Day 1. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. Macroscopic post mortem examination revealed abnormalities of the clitoral glands (tan foci) in two out of six animals. In one animal, the caecum was distended with gas. Macroscopic post mortem examination of the other animals at termination did not reveal any test material related abnormalities.

The acute oral LD50 value in Wistar Han rats was determined to exceed 2000 mg/kg bw.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute oral toxicity.