4-mesyl-2-nitrotoluene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 April - 21 July 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, no restrictions, fully adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

430-550-0

EC Name:

-

Cas Number:

1671-49-4

Molecular formula:

C8H9NO4S

IUPAC Name:

4-methanesulfonyl-1-methyl-2-nitrobenzene

Details on test material:

- Physical state: white solid
- Storage condition of test material: ambient temperature in the dark

Test animals

Species:

rat

Strain:

other: Alpk:APfSD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 8-12 weeks
- Weight at study initiation: 266-404 g (males), 193-263 g (females)
- Fasting period before study: overnight prior to dosing
- Housing: maximum of 5 per cage, sexes separately in cages suitable for rats of this strain and weight range expected during the course of the study
- Diet: RMI ad libitum (except during overnight fast)
- Water: mains water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22±3°C
- Humidity: 30-70%
- Air changes: minimum of 15 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 2 June 1999 To: 21 July 1999

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1%

Details on oral exposure:

Dose levels prepared by adjusting concentration of the dosing preparations. The volume of the dose was calculated for each animal according to its weight at the time of dosing. A standard volume of 10 mL/kg bodyweight of the dosing preparation was dosed.

Doses:

200, 500, 1000 or 2000 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed twice on day 1 and once per day thereafter. Weighed prior to fasting (day -1), immediately before dosing (day 1) and on days 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: none

Statistics:

The acute oral median lethal dose was estimated from mortality data by logistic regression using nominal dose values. Confidence limits calculated using a likelihood ratio interval (Williams DA, 1986. Interval Estimation of the Median Lethal Dose. Biometrics 42, 641-645).

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1 426 mg/kg bw

Based on:

test mat.

Remarks:

2479

95% CL:

971

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

933 mg/kg bw

Based on:

test mat.

Remarks:

1259

95% CL:

692

Mortality:

200 or 500 mg/kg - no deaths; 1000 mg/kg - 1 male and 3 females killed in extremis on day 2; 2000 mg/kg - 4 males and all 5 females found dead or killed in extremis between days 1 and 3.

Clinical signs:

other: 200 mg/kg - signs of slight systemic toxicity (including tip-toe gait, lachrymation, salivation, subdued behaviour, upward curvature of spine and breathing irregular) with complete recovery by day 2. 500 mg/kg - signs of slight or moderate toxicity (inclu

Gross pathology:

No treatment-related findings at 500 mg/kg. In the other groups there was a reduction in testes and epididymes of some males, changes to the stomach/abnormal stomach contents and pallor of liver and kidneys, speckling of the thymus and non-specific staining around the nose and mouth.

Any other information on results incl. tables

Table 1: Mortality data

Dose Level	Day Number	Number of Deaths
(mg/kg)		Male	Female
200	Total at day 15	0/5	0/5
500	Total at day 15	0/5	0/5
1000	2	1	3
	Total at day 15	1/5	3/5
2000	1	0	1
	2	3	4
	3	1	0
	Total at day 15	4/5	5/5

 

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of the test substance was estimated to be 1426 mg/kg (95% confidence limits 971-2479) to male rats and 933 mg/kg (95% confidence limits 692-1259) to female rats.

Executive summary:

Groups of 5 male and 5 female Alpk:APfSD rats received a single oral dose of 200, 500, 1000 or 2000 mg/kg of the test substance. The animals were assessed daily for the following 14 days for any signs of systemic toxicity and their bodyweights recorded at intervals throughout the study. Animals in extremis and those surviving to the end of the study were killed and, together with those found dead, subjected to a macroscopic examination post mortem. Surviving animals showed signs of slight to moderate toxicity which were resolving towards the end of the experimental period. Findings at post mortem were restricted to males dosed with 1000 mg/kg and above and included reduced testicular and epididymal weights. The acute oral LD₅₀of the test substance was estimated to be 1426 mg/kg (95% confidence limits 971-2479) to male rats and 933 mg/kg (95% confidence limits 692-1259) to female rats.