Tetramethylammonium hydrogen phthalate

Endpoint summary

Description of key information

Reliable acute studies for the oral and dermal route are available, performed according to EC/ OECD guidelines and GLP principles. The acute oral LD50 of TMAP in the rat was calculated to be 105 (88 - 126) mg/kg bw. No mortalities were observed in the dermal toxicity test at 2000 mg/kg bw. It is of note that TMAP is the same test substance as TMHP (tetramethylammonium hydrogen phthalate).

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:

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.

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

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

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.

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.

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)

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

100 mg/kg bw

Quality of whole database:

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 (Klimisch 2).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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

Study period:

June 1987-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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

yes

Remarks:

no information on test substance purity

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

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 ten to fourteen weeks old
- Weight at study initiation: males 234 - 269g, females 208 - 232g
- Fasting period before study: no
- Housing: solid-floor polypropylene cages with sawdust bedding; during exposure housed individually after in groups of 5 by sex.
- 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 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Humidity (%): 60 - 68
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 16 June 1987 To: 30 June 1987

Type of coverage:

semiocclusive

Vehicle:

other: moistened with distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 cm x 12 cm (clipped free of hair).
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: surgical gauze measuring 7 cm x 4 cm was placed over the treatment area and semi-occluded with a double layer of elastic adhesive bandage {ELASTOPLAST) wrapped around the trunk of the rat.

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin and surrounding hair was wiped with moist absorbant paper to remove any residual test material .
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for overt signs of toxicity and mortality 1 and 4· hours after dosing and subsequently at least once daily for fourteen days. Individual bodyweights were recorded on the day of treatment (day 0) and on days seven and fourteen.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality

Clinical signs:

other: No signs of systemic toxicity or skin irritation were noted during the study period.

Gross pathology:

No abnormalities were noted at necropsy of animals killed at the end of the study period.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on an acute dermal toxicity test with TMAP faccording to OECD guideline 402, the acute dermal median lethal dose (LD50) of TMAP in the rat was found to be greater than 2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study in rat performed according to OECD guideline 402, TMAP was tested in 5 rats/sex at the limit dose of 2000 mg/kg bw (semi-occluded application) for 24 hours. No deaths occurred. No signs of systemic toxicity or skin irritation were noted during the study. The animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy of animals killed at the end of the study period. The acute dermal median lethal dose (LD50) of the test material in the rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

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 (Klimisch 2).

Additional information

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. All surviving animals 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.

In an acute dermal toxicity study in rat performed according to OECD guideline 402, TMAP was tested in 5 rats/sex at the limit dose of 2000 mg/kg bw (semi-occluded application) for 24 hours. No deaths occurred. No signs of systemic toxicity or skin irritation were noted during the study. The animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy of animals killed at the end of the study period. The acute dermal LD50 of the test material in the rat was found to be greater than 2000 mg/kg bodyweight.

It is of note that TMAP is the same test substance as TMHP (tetramethylammonium hydrogen phthalate).

Justification for selection of acute toxicity – oral endpoint
One study available.

Justification for selection of acute toxicity – dermal endpoint
One study available.

Justification for classification or non-classification

Based on the calculated LD50 of 100 mg/kg bw/day for females in the acute oral toxicity study, tetramethylammonium hydrogen phthalate is classified category 3 for oral toxicity according to Regulation (EC) No 1272/2008 on clasification , labelling and packaging of substances and mixtures.

Based on the absence of mortality at 2000 mg/kg bw in the acute dermal toxicity study, tetramethylammonium hydrogen phthalate is not classified for dermal toxicity according to Regulation (EC) No 1272/2008 on clasification , labelling and packaging of substances and mixtures.