Quaternary ammonium compounds, C12-14 (even numbered) alkyl(hydroxyethyl)dimethyl, C12 alkylbis(hydroxyethyl)methyl, chlorides and amines, C12-14 (even numbered) alkyldimethyl, chlorides

Endpoint summary

Description of key information

Based on the results of the read across study, the oral LD50 value for the test substance is considered at 207 mg a.i./kg bw respectively; indicative of moderate acute toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

From 12 June, 1986 to 13 September, 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

KL2 due to RA

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: Category 3 as per CLP

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

226 mg/kg bw

Based on:

act. ingr.

95% CL:

ca. 207 - ca. 245

Remarks on result:

other: Category 3 as per CLP

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:

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 mouth, respiratory distress, ataxia, lethargy, salivation and hypothermia. Animals in the 908 mg/kg bw also showed clear ocular discharge and tremors.

Body weight:

No effect

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.

Mortality and other observations

Table 1.                           Table for Acute Toxicity
Dose [mg a.s./kgbw]	Number of dead / number of investigated	Time of death (range)	Observations
0	0/10		No findings
169	0/10		Four females had wet yellow anogenital staining early in the study period. One of these also had diarrhea and one male had slight dried brown staining around the mouth. There were no other findings.
205	3/10	Found dead day 3	Anogenital staining, diarrhea, brown staining around the mouth, evidence of respiratory distress (respiratory rales and/or bradypnea), ataxia, lethargy, salivation, and hypothermia
248	7/10	Found dead day 1-3	Similar, but higher incidence.
300	5/5	Found dead day 1-3	diarrhea, wet yellow and/or brown urogenital staining, and respiratory distress (rales and bradypnea). Ataxia and lethargy were noted for three of the five rats. Other findings in this group included clear ocular discharge, hypothermia, tremors and various stains around the mouth
LD50 value	Male & female combined: 226 (207-245) mg a.i./kgbw

Interpretation of results:

other: Category 3 based on CLP criteria

Conclusions:

Based on the results of the read across study, the acute oral LD50 of the read across substance in Sprague-Dawley rats is considered to be 684 mg test substance/kg bw (i.e., equivalent to 226 mg a.i./kg bw)

Executive summary:

A study was conducted to determine the acute oral toxicity of the read across 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 read across 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 read across 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). Based on the results of the read across study, similar LD50 value is expected for the test substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

207 mg/kg bw

Quality of whole database:

The information requirement for this tonnage band is sufficiently met with the available data.

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

Reason / purpose for cross-reference:

data waiving: supporting information

Clinical signs:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral

A study was conducted to determine the acute oral toxicity of the read across 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 read across 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 read across 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). Based on the results of the read across study, similar LD50 value is expected for the test substance.

Based on the above study, the biocide assessment report available from RMS Italy on Coco TMAC (ECHA assessment report, 2016), selected the lowest acute oral LD50 value at 207 mg a.i./kg bw. They further stated that the clinical signs were mainly due to gastrointestinal disturbance, respiratory distress, ataxia, lethargy, salivation and hypothermia. Therefore, in line with the biocides assessment report, the oral LD50 value of 207 mg a.i./kg bw has been considered further for hazard/risk assessment.

Dermal

In accordance with Annex VII, Section 8.5, Column 2, additional acute toxicity study for dermal route does not need to be conducted because the substance is classified as corrosive to the skin.  

Inhalation

In accordance with Annex VII, Section 8.5, Column 2, additional acute toxicity study for inhalation route does not need to be conducted because the substance is classified as corrosive to the skin. Further, the substance has a low predicted vapour pressure (VP <3.4E-04 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 oral LD50 value from the read across study, the test substance warrants an ‘Acute Tox. 3; H301: toxic if swallowed’ classification for the oral route according to EU CLP criteria (Regulation EC 1272/2008).