Tetramethylammonium hydrogen phthalate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June-July 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles. Test substance only indicated by abbreviation; no information on test substance purity.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

no information on test substance purity

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetramethylammonium hydrogen phthalate

EC Number:

416-900-5

EC Name:

Tetramethylammonium hydrogen phthalate

Cas Number:

79723-02-7

Molecular formula:

C12H17NO4

IUPAC Name:

tetramethylazanium 2-carboxybenzoate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): TMAP
- Physical state: white crystalline powder
- Storage condition of test material: room temperature in sealed container

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna (UK) Limited, Wyton, Huntingdon, Cambridgeshire
- Age at study initiation: approximately five to eight weeks old
- Weight at study initiation: males 134 - 159g; females 130 - 159g
- Fasting period before study: overnight
- Housing: in groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding
- Diet: free access to food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.)
- Water: free access to mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 60 - 70
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 12 June 1987 to 17 July 1987

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

50, 85, 146 and 250 mg/kg bw

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: observations 1 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded on the day of treatment (day 0), days 7 and 14, and at death.
- Necropsy of survivors performed: yes
Concentration range in the main study is based on a range-finding study.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

100 mg/kg bw

Based on:

test mat.

95% CL:

81 - 124

Remarks on result:

other: Lowest LD50 compared to total or males separately.

Mortality:

Male animals:
* 50 mg/kg bw: 0 of 5
* 85 mg/kg bw: 1 of 5
* 146 mg/kg bw: 4 of 5
* 250 mg/kg bw: 5 of 5

Female animals:
* 50 mg/kg bw: 0 of 5
* 85 mg/kg bw: 1 of 5
* 146 mg/kg bw: 5 of 5
* 250 mg/kg bw: 5 of 5

Majority of deaths within 1h of treatment. All other deaths within 4h of treatment.

Clinical signs:

other: Signs of toxicity related to dose levels: Surviving animals from all dose groups showed hunched posture, pilo-erection, decreased respiratory rate and lethargy 1 and 4 hours after dosing. Ptosis was also commonly noted in animals treated with 85 mg/kg bw

Gross pathology:

Effects on organs:
One surviving female treated with 85 mg/kg bw showed abnormally red lungs with small and pale liver and spleen and pale kidneys. Ulceration of the gastric mucosa was also noted.

All other surviving animals showed no uncommonly observed abnormalities at necropsy at the end of the study.

Other findings:

Common abnormalities noted at necropsy of decedents were abnormally red lungs, dark livers, kidneys and spleen and sloughing of the gastric mucosa. Congestion of the small intestines was also occasionally noted.

Any other information on results incl. tables

The acute oral median lethal doses (LD50) and 95% confidence limits of TMAP in the rat were calculated by the method of Weil to be:

* 105 (88 - 126) mg/kg bw (all animals)

* 111 (82 - 151) mg/kg bw (males only)

* 100 (81 - 124) mg/kg bw (females only)

Applicant's summary and conclusion

Interpretation of results:

other: cat. 3

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on an acute oral toxicity test with TMAP, following OECD guideline 401, the acute oral LD50 of TMAP in the rat was calculated to be 100 (81-124) mg/kg bodyweight.

Executive summary:

In an acute oral toxicity study in rat performed according to OECD guideline 401, TMAP was tested in 5 rats/sex at dose levels of 50, 85, 146 and 250 mg/kg bw. The majority of deaths occurred within one hour of treatment or were noted four hours after treatment. Principal signs of toxicity, noted shortly after dosing, were hunched posture, pilo-erection, lethargy and decreased respiratory rate. Ptosis was also noted in animals treated with 85 mg/kg and above. Isolated or occasional signs of ataxia or clonic convulsions were also noted. All surviving animals were normal one to two days after dosing and showed expected gains in bodyweight over the study period. One surviving female treated with 85 mg/kg also showed abnormally red lungs, with small and pale liver and spleen and pale kidneys with ulceration of the gastric mucosa. All other surviving animals showed no abnormalities. The acute oral LD50 of the test material was calculated to be 100 (81-124) mg/kg bodyweight.