Quaternary ammonium compounds, coco alkyltrimethyl, chlorides

Endpoint summary

Description of key information

In line with the biocides assessment report, the oral and dermal LD50 values of the test substance was considered to be at 207 and 429 mg a.i./kg bw respectively, suggesting of moderate acute toxicity potential. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 7 Novermber, 1986 to 4 December, 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

OECD 401 Guideline for testing of chemicals, 1981

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Sprague-Dawley CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

Sprague-Dawley CFY rats (5-8 weeks old): 23 males and females each sex
Bodyweight: 127-153 g (males), 121-156 g (females)

The animals were housed in groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding. With the exception of an overnight fast immediately before dosing and for approximately two hours after dosing, free access to mains drinking water and food was allowed throughout the study. The animal room was maintained at a temperature of 19 - 23 C and relative humidity of 45 - 65%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

Range-finding test: 0, 500, 1000, 2000 mg/kg bw
Main study: 0, 1000, 1260, 1587, 2000 mg/kg bw

No. of animals per sex per dose:

RF test: 1
Main study: 5

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 225 mg/kg bw

Based on:

test mat.

95% CL:

ca. 1 084 - ca. 1 384

Remarks on result:

other: i.e., equivalent to 428.8 mg a.i./kg bw

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 130 mg/kg bw

Based on:

test mat.

95% CL:

ca. 919 - ca. 1 390

Remarks on result:

other: i.e., equivalent to 395.5 mg a.i./kg bw

Key result

Sex:

female

Dose descriptor:

LD50

Remarks:

mg/kg bw

Effect level:

ca. 1 320 mg/kg bw

Based on:

test mat.

95% CL:

ca. 1 065 - ca. 1 637

Remarks on result:

other: i.e., equivalent to 462 mg a.i./kg bw

Mortality:

One male treated with 1000 mg/kg was found dead one hour after treatment. All other deaths were noted one to five days after treatment. Major signs of toxicity noted were hunched posture, pilo-erection, lethargy, decreased respiratory rate, ptosis and diarrhoea. Occasional signs of ataxia were noted in high dose group animals.

Clinical signs:

other: Major signs of toxicity noted in all dose groups on the day of dosing were hunched posture, piloerection, lethargy, decreased respiratory rate, ptosis and diarrhea. Occasional signs of ataxia were noted in high dose group animals during this period. Other

Gross pathology:

Major findings at necropsy of decedents were abnormally red lungs, dark or mottled livers, hemorrhage, ulceration or sloughing off of the gastric mucosa and congestion of the small intestine. Necropsy of animals killed at the end of the study showed scattered white thickening on areas of the non-glandular region of the stomach.

Range-finding study

The mortality data were summarized as follows:

 

Dose level (mg/kg)	Deaths on day						Total deaths	%
	0	1	2	3	4	5
500	0	0	0	0	0	0	0/2	0
1000	0	0	0	0	0	0	0/2	0
2000	0	0	2	-	-	-	2/2	100

= all animals dead

The mortality data indicated an oral LD50 between 1000 and 2000 mg/kg.

 

Main Study

The mortality data were summarized as follows:

 

Dose level (mg/kg)	Deaths
	Male	Female	Total	%
1000	3/5	0/5	3/10	30
1260	2/5	2/5	4/10	40
1587	5/5	5/5	10/10	100
2000	5/5	5/5	10/10	100

Interpretation of results:

other: Category 4 based on CLP criteria

Conclusions:

Under study conditions, the LD50 value of the test substance was determined at 1225 mg/kg bw (i.e., equivalent to 428.8 mg a.i./kg bw) for males and females rats combined.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance, Coco TMAC (35% in water), in Sprague-Dawley CFY strain rats according to OECD 401 Guideline, in compliance with GLP. Following a range-finding study, four groups, each of ten fasted animals (5 males and 5 females) were given a single oral dose of undiluted test substance, at dose levels of 0, 1000, 1260, 1587 and 2000 mg/kg bw. One male treated with 1000 mg/kg bw was found dead one hour after treatment. All other deaths were noted one to five days after treatment. Major signs of toxicity noted were hunched posture, pilo-erection, lethargy, decreased respiratory rate, ptosis and diarrhoea. Occasional signs of ataxia were noted in high dose group animals. Less frequent signs of pallor of the extremities, diuresis, red/brown staining around the snout and chromodacryorrhoea were noted in animals treated with 1260 mg/kg bw and above. All surviving animals were normal two to six days after treatment. With the exception of surviving males treated with 1260 mg/kg which showed reduced bodyweight gains on day seven, all surviving animals showed expected bodyweight gain over the study period. Major findings at necropsy of decedents were abnormally red lungs, dark or mottled livers, haemorrhage, ulceration or sloughing of the gastric mucosa and congestion of the small intestine. Necropsy of animals killed at the end of the study showed scattered white thickening on areas of the nonglandular region of the stomach. The acute oral median lethal dose (LD50) and 95% confidence limits were found to be: (1) all animals: 1225 (1084 - 1384) mg/kg bw (2) males only: 1130 (919 - 1390) mg/kg bw (3) females only: 1320 (1065 - 1637) mg/kg bw. Under study conditions, the LD50 value of the test substance was determined at 1225 mg/kg bw (i.e., equivalent to 428.8 mg a.i./kg bw) for males and females rats combined (Jones, 1987).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 12 June, 1986 to 13 September, 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

One animal in the lowest dose group was not observed for clinical findings at 4 h after dosing on Day 0. this deviation does not affect the scientific validity or integrity of the study.

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

One animal in the lowest dose group was not observed for clinical findings at 4 h after dosing on Day 0. this deviation does not affect the scientific validity or integrity of the study.

Qualifier:

according to guideline

Guideline:

other: Toxic Substances Control Act (TSCA) Health Effects Test Guidelines

Deviations:

yes

Remarks:

One animal in the lowest dose group was not observed for clinical findings at 4 h after dosing on Day 0. this deviation does not affect the scientific validity or integrity of the study.

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: Charles River Breeding Laboratories, Inc., Portage, Michigan
- Weight at study initiation: 205-262 g
- Fasting period before study: 18 h
- Housing: Individually housed in wire-mesh cages
- Diet: Purina certified rodent chow # 5002, ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: Minimum 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): more than 40%
- Photoperiod (h dark/h light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.93 mL/kg

Doses:

0, 512, 620, 750 and 908 mg/kg bw .

No. of animals per sex per dose:

Five animals per sex per dose except for the highest dose which has only 5 males.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of clinical observation: 1, 2.5 and 4 h after dosing on Day 0 and subsequently once daily for 14 d.
- Frequency of weighing: On Days 0, 7 and 14
- Necropsy of survivors performed: Yes
- Examinations performed: Clinical signs, body weight and gross pathological examination.

Statistics:

LD50 values and slopes (with 95% confidence limit) were calculated by method of Litchfield and Wilcoxon.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

684 mg/kg bw

Based on:

test mat.

95% CL:

ca. 629 - ca. 743

Remarks on result:

other: i.e., equivalent to 226 mg a.i./kg bw with 95% confidence limits of 207-245 mg a.i./kg bw

Mortality:

There was no mortality in the 512 mg/kg bw group while 3 out of 10 and 7 out of 10 rats died in the 620 and 750 mg/kg bw groups, respectively. All the five animals died receiving the highest tested dose of 908 mg/kg bw.

Clinical signs:

other: Four males in the 512 mg/kg bw group had yellowish anogenital staining during early study period and one of these animals had diarrhoea. Several animals in the 620, 750 and 908 mg/kg bw showed anogenital staining, diarrhoea, brown staining around the mout

Gross pathology:

Changes were observed in the adrenal glands, brain, kidneys, stomach and intestines for more than one and half of all rats died during study. Abnormalities in the liver were found in of 7/15 of the dead rats. No significant changes for all tissues examined for rats that were terminally sacrificed, including control group.

In the range-finding study, all the rats dosed at 1000, 1500 and 2000 mg/kg bw died while rats dosed at 500 mg/kg bw survived.

Interpretation of results:

other: Category 3 based on CLP criteria

Conclusions:

Under the study conditions, the acute oral LD50 of the test substance in Sprague-Dawley rats was determined to be 684 mg/kg bw (or 226 mg a.i./kg bw) with 95% confidence limits of 629 -743 mg/kg bw (or 207-245 mg a.i./kg bw)

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance, Coco TMAC (33% active in water), in Sprague-Dawley rats according to OECD 401 and EPA OPP 81-2 Guidelines, in compliance with GLP. Groups of 10 fasted animals (five males and five females per dose except for five males only at the highest dose) were administered 0, 512, 620, 750 or 908 mg/kg bw of the test substance (i.e., equivalent to 0, 169, 205, 248 and 300 mg a.i./kg bw) via the oral route. The animals were observed for 14 days after dosing and then sacrificed and subjected to gross pathological examination. There was no mortality in the 512 mg/kg bw (or 169 mg a.i./kg bw) group while 3 out of 10 and 7 out of 10 rats died in the 620 mg/kg bw (or 205 mg a.i./kg bw) and 750 mg/kg bw (or 248 mg a.i./kg bw) groups, respectively. All five animals in the highest dose group (908 mg/kg bw or 300 mg a.i./kg bw) died. Under the study conditions, the acute oral LD50 of the test substance in Sprague-Dawley rats was determined to be 684 mg/kg bw (or 226 mg a.i./kg bw) with 95% confidence limits of 629 -743 mg/kg bw (or 207-245 mg a.i./kg bw) (Naas, 1987).  

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

207 mg/kg bw

Quality of whole database:

Guideline and GLP compliant studies; LD50 value in line with the key value selected in the biocides dossier I

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

other:

Reason / purpose for cross-reference:

data waiving: supporting information

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:

From 22 February, 1988 to 24 March, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Toxic Substances Control Act (TSCA) acute dermal toxicity guideline

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mochican Valley Rabbitry, Loidonville, Ohio
- Weight at study initiation: 2140 to 2990 g
- Housing: individual suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified rabbit chow # 5322, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Minimum 7 d

ENVIRONMENTAL CONDITIONS
- Humidity (%): 49-74%
- Photoperiod (h dark / h light): 12 h / 12 h

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: Shaved intact dorsal skin
- % coverage: 20%
- Type of wrap if used: Test substance was applied under gauze binders that were secured with non-irritating tape.

Duration of exposure:

24 h

Doses:

0, 520, 1020 and 2000 mg/kg bw.

No. of animals per sex per dose:

Five animals per sex per test group, three animals per sex in control group.

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: Animals were observed at 1, 3 and 4 h post-dosing on Day 0 and twice daily for mortality and once daily for clinical observations for 14 d. Application sites were examined for erythema, oedema and other dermal findings at 30−60 min after bandage removal and daily thereafter for 13 d. Erythema and oedema were graded according to Draize method.
- Frequency of observations and weighing: Day 0, 7 and 14
- Necropsy of survivors performed: yes

Statistics:

LD50 and slopes (with 95% confidence limits) were calculated by method of Litchfield and Wilcoxon.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 300 mg/kg bw

Based on:

test mat.

95% CL:

ca. 800 - ca. 1 900

Remarks on result:

other: i.e., equivalent to 429 mg a.i./kg bw

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 900 mg/kg bw

Based on:

test mat.

95% CL:

ca. 1 500 - ca. 2 400

Remarks on result:

other: i.e., equivalent to 627 mg a.i./kg bw

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 600 mg/kg bw

Based on:

test mat.

95% CL:

ca. 1 200 - ca. 2 100

Remarks on result:

other: i.e., equivalent to 528 mg a.i./kg bw

Mortality:

Control: 0/6 animals
520 mg/kg bw: 0/10 animals
1020 mg/kg bw: 2/5 males and 0/5 females
2000 mg/kg bw: 4/5 males and 3/5 females

Clinical signs:

other: Lethargy and ataxia were major clinical findings. Other findings included hypothermia, decreased respiratory rate, laboured respiration, nasal discharge, decreased defecation, emaciation, red staining around the mouth, diarrhoea.

Gross pathology:

Treatment-related abnormality on the application sites of all rabbits. No substance-related internal abnormalities in rabbits that died during study or terminally sacrificed.

Other findings:

Test substance induced moderate to severe erythema and oedema with other significant dermal findings such as necrosis, desquamation, scabbing, eschar, exfoliation, fissuring and blenching. Subcutaneous haemorrhage was present on the application sites of one rabbit in the 2000 mg/kg bw group that survived and all animals that died.

Only (systemic) pathology observed in animals sacrificed at termination were kidney abnormalities (pale, reddened, pitted) in 5/21 of the terminally sacrificed dosed rabbits. Pale kidneys were also observed for one female in the control group. The skin of the animals that died showed eschar, subcutaneous haemorrhage, blanching and thickening. Internal abnormalities included hemorrhagic thymus glands (6/9) (typical agonal change), red foci or dark red area in the stomach (3/9), brain haemorrhages (3/9) and liver soft or pale and soft (2/9). No internal abnormalities were observed among rabbits that died which could be attributed to the test substance. There were no test substance related internal changes for rabbits that were terminally sacrificed.

Considering the generally low dermal absorption of Coco TMAC (<10% in Bartnik and Wingen, 1979 study), it is likely that severe corrosive effects upon the 24 h exposure of the concentrated product were more cause to the death of the animals, than real systemic toxicity. This is supported by the relatively limited observations on internal organs upon necropsis of the animals that died. The most commonly observed internal abnormalities were hemorrhagic thymus glands (6/9), which is a typical agonal change, and likely not a specific sign of toxicity.

Mortality and other observations

Table 1.                           Table for Acute Toxicity
Dose [mg a.s./kg bw]	Number of dead / number of investigated	Time of death (range)	Observations
0	0/6		Pale kidneys were observed for one female in the control group. No other changes were noted for control group.
172	0/10		Eschar and thickening on the application site. Decreased defecation primarily early in the study period(7/10). Also observed in one or two animals: clear wet matting around the mouth, clear wet ventral abdominal matting, clear nasal discharge, diarrhea, scabbing on the right hind leg and hair loss and desquamation in the urogenital area.
337	2/10	Found dead morning 1^stand 2^ndday	Eschar, subcutaneous hemorrhage, blanching and thickening were noted on the application sites of rabbits that died, and Eschar and thickening on the application site of the other animals. Decreased defecation primarily early in the study period(4/10). Also observed in one or two animals: clear wet matting around the mouth, clear wet ventral abdominal matting, clear nasal discharge, diarrhea, scabbing on the right hind leg and hair loss and desquamation in the urogenital area.
660	7/10	Found dead morning 1^stday.	Lethargy, ataxia, laboured respiration, purulent nasal discharge on day 1, emaciated appearance. Necrosis, desquamation, scabbing, eschar, exfoliation, fissuring and blanching. Also, subcutaneous hemorrhage was present on the application sites of one rabbit in the 2000 mg/kg group that survived and all animals that died. No internal abnormalities were observed among rabbits that died which could be Attributed to the test material.
LD50value	Male & female combined: 528 (396 – 693) mg a.s/kg bw

For further details on result tables, kindly refer to the attached background material section of the IUCLID.

Interpretation of results:

other: Category 3 based on CLP criteria

Conclusions:

Under the study conditions, the acute dermal LD50 for male and female albino rabbits were determined to be 1,300 mg/kg bw (i.e., equivalent to 429 mg a.i./kg bw) and 1,900 mg/kg bw (i.e., equivalent to 627 mg a.i./kg bw) respectively, and the combined dermal LD50 was determined to be 1,600 mg/kg bw (i.e., equivalent to 528 mg a.i./kg bw).

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance, Coco TMAC (33% active in water), in albino rabbits according to OECD 402 Guideline, in compliance with GLP. Semi-occlusive patches of the test substance at 0, 520, 1,020 or 2,000 mg/kg bw (i.e., equivalent to 0, 172, 337 and 660 mg a.i./kg bw) was applied to the shaved, intact skin of groups of 10 rabbits (five per sex) for 24 h. Animals were observed at 1, 3 and 4 h post-dosing. Following the 24 h exposure period, animals were observed for mortality, clinical signs and skin response for 14 d. There was no mortality in the control or 520 mg/kg bw (or 172 mg a.i./kg bw) group. Two males died in the 1,020 mg/kg bw (or 337 mg a.i./kg bw) group while 4 males and 3 females died in the 2,000 mg/kg bw (or 660 mg a.i./kg bw) group. Under the study conditions, the acute dermal LD50 for male and female albino rabbits were determined to be 1,300 mg/kg bw (i.e., equivalent to 429 mg a.i./kg bw) and 1,900 mg/kg bw (i.e., equivalent to 627 mg a.i./kg bw) respectively, and the combined dermal LD50 value for males and females was determined to be 1,600 mg/kg bw (i.e., equivalent to 528 mg a.i./kg bw). Considering the generally low dermal absorption potential of Coco TMAC (<10% in Bartnik and Wingen, 1979 study), the observed systemic effects and mortality were attributed to the severe corrosive properties of the test substance following 24 h exposure rather than real systemic toxicity. This is supported by the relatively limited observations on internal organs upon necropsis of the animals that died (Naas, 1988).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

429 mg/kg bw

Quality of whole database:

Guideline and GLP compliant study; LD50 value in line with the key value selected in the biocides dossier

Additional information

Oral  

Study 1: A study was conducted to determine the acute oral toxicity of the test substance, TMAC C (33% active in water), in Sprague-Dawley rats according to OECD 401 and EPA OPP 81-2 Guidelines, in compliance with GLP. Groups of 10 fasted animals (five males and five females per dose except for five males only at the highest dose) were administered 0, 512, 620, 750 or 908 mg/kg bw of the test substance (i.e., equivalent to 0, 169, 205, 248 and 300 mg a.i./kg bw) via the oral route. The animals were observed for 14 days after dosing and then sacrificed and subjected to gross pathological examination. There was no mortality in the 512 mg/kg bw (or 169 mg a.i./kg bw) group while 3 out of 10 and 7 out of 10 rats died in the 620 mg/kg bw (or 205 mg a.i./kg bw) and 750 mg/kg bw (or 248 mg a.i./kg bw) groups, respectively. All five animals in the highest dose group (908 mg/kg bw or 300 mg a.i./kg bw) died. Under the study conditions, the acute oral LD50 of the test substance in Sprague-Dawley rats was determined to be 684 mg/kg bw (or 226 mg a.i./kg bw) with 95% confidence limits of 629 -743 mg/kg bw (or 207-245 mg a.i./kg bw) (Naas, 1987).   

Study 2:A study was conducted to determine the acute oral toxicity of the test substance, TMAC C (35% active in water), in Sprague-Dawley CFY strain rats according to OECD 401 Guideline, in compliance with GLP. Following a range-finding study, four groups, each of ten fasted animals (5 males and 5 females) were given a single oral dose of undiluted test substance, at dose levels of 0, 1000, 1260, 1587 and 2000 mg/kg bw. One male treated with 1000 mg/kg bw was found dead one hour after treatment. All other deaths were noted one to five days after treatment. Major signs of toxicity noted were hunched posture, pilo-erection, lethargy, decreased respiratory rate, ptosis and diarrhoea. Occasional signs of ataxia were noted in high dose group animals. Less frequent signs of pallor of the extremities, diuresis, red/brown staining around the snout and chromodacryorrhoea were noted in animals treated with 1260 mg/kg bw and above. All surviving animals were normal two to six days after treatment. With the exception of surviving males treated with 1260 mg/kg which showed reduced bodyweight gains on day seven, all surviving animals showed expected bodyweight gain over the study period. Major findings at necropsy of decedents were abnormally red lungs, dark or mottled livers, haemorrhage, ulceration or sloughing of the gastric mucosa and congestion of the small intestine. Necropsy of animals killed at the end of the study showed scattered white thickening on areas of the non-glandular region of the stomach. The acute oral median lethal dose (LD50) and 95% confidence limits were found to be: (1) all animals: 1225 (1084 - 1384) mg/kg bw (2) males only: 1130 (919 - 1390) mg/kg bw (3) females only: 1320 (1065 - 1637) mg/kg bw. Under study conditions, the LD50 value of the test substance was determined at 1225 mg/kg bw (i.e., equivalent to 428.8 mg a.i./kg bw) for males and females rats combined (Jones, 1987).

The biocide assessment report available from RMS Italy on TMAC C, concluded the lowest oral LD50 for ATMAC and TMAC (also known as TMAC C) at 207 mg a.i./kg bw. This was based on studies submitted by Lonza Cologne GmbH and Akzo Nobel Surface Chemistry AB (Naas, 1987). The clinical signs observed in these studies were mainly attributed due to gastrointestinal disturbance, respiratory distress, ataxia, lethargy, salivation and hypothermia (ECHA biocides assessment report, 2016).

Therefore, considering that the oral LD50 values are in the same range, the lower LD50 value of 207 mg/kg bw/day (which also matches with the lower confidence limit calculated for the Nash 1987 study) can be considered for further hazard assessment in order to be in line with the biocides assessment report.

  

Dermal 

A study was conducted to determine the acute dermal toxicity of the test substance, TMAC C (33% active in water), in albino rabbits according to OECD 402 Guideline, in compliance with GLP. Semi-occlusive patches of the test substance at 0, 520, 1,020 or 2,000 mg/kg bw (i.e., equivalent to 0, 172, 337 and 660 mg a.i./kg bw) was applied to the shaved, intact skin of groups of 10 rabbits (five per sex) for 24 h. Animals were observed at 1, 3 and 4 h post-dosing. Following the 24 h exposure period, animals were observed for mortality, clinical signs and skin response for 14 d. There was no mortality in the control or 520 mg/kg bw (or 172 mg a.i./kg bw) group. Two males died in the 1,020 mg/kg bw (or 337 mg a.i./kg bw) group while 4 males and 3 females died in the 2,000 mg/kg bw (or 660 mg a.i./kg bw) group. Under the study conditions, the acute dermal LD50 for male and female albino rabbits were determined to be 1,300 mg/kg bw (i.e., equivalent to 429 mg a.i./kg bw) and 1,900 mg/kg bw (i.e., equivalent to 627 mg a.i./kg bw) respectively, and the combined dermal LD50 value for males and females was determined to be 1,600 mg/kg bw (i.e., equivalent to 528 mg a.i./kg bw). Considering the generally low dermal absorption potential of TMAC C (<10% in Bartnik and Wingen, 1979 study), the observed systemic effects and mortality were attributed to the severe corrosive properties of the test substance following 24 h exposure rather than real systemic toxicity. This is supported by the relatively limited observations on internal organs upon necropsis of the animals that died (Naas, 1988).  

The biocide assessment report available from RMS Italy on TMAC C, concluded the lowest oral LD50 for ATMAC and TMAC (also known as TMAC C) at 429 mg a.i./kg bw. This was based on studies submitted by Lonza Cologne GmbH and Akzo Nobel Surface Chemistry AB (Naas, 1988). (ECHA biocides assessment report, 2016).

Therefore, considering that the dermal LD50 value of 429 mg a.i./kg bw matches the lower value determined in Naas, 1988 study as well, this LD50 value can be considered for further hazard assessment in order to be consistent with the biocides assessment report.

Inhalation

In accordance with Annex VII, Section 8.5, Column 2, acute toxicity study for inhalation route does not need to be conducted because the substance is classified as corrosive to the skin.The substance has a low vapour pressure (VP = <5.8E-3 Pa at 25°C), which is below the cut-off of 0.01 Pa set for defining low volatility substances, as per the ECHA Guidance R.7a. Therefore, due to its low VP, it is unlikely that it will form inhalable dust, mist or fumes when handled and used in solid form. In case inhalable forms of the substance (either pure or in aqueous solutions) are created under particular conditions (e.g., spraying, elevated temperature/pressure), appropriate risk management measures such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation.  

Justification for classification or non-classification

Based on the acute toxicity data (oral and dermal LD50 of 207 and 429 mg a.i./kg bw, respectively), the test substance warrants an ‘Acute Tox.3, H301: toxic if swallowed’ for the oral route and ‘Acute Tox.3, H311: toxic in contact with skin’ for the dermal route, classifications according to EU CLP criteria (Regulation EC 1272/2008).

In addition, for the inhalation route, although the test substance is classified to be corrosive (see section 5.3) and this drives its mechanism of action of toxicity, its inherent low vapour pressure prohibits the occurrence of respiratory irritation or corrosion by vapour. Therefore, it does not warrant additional labelling as: EUH071 — ‘Corrosive to the respiratory tract’ according to EU CLP criteria (Regulation EC 1272/2008).  

 

Further, the available data does not show an indication that classification for STOT-SE cat 1 or 2 is indicated. For STOT-SE Cat 3, the test substance or other QAS substances in general are not known to be narcotic.