Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, acetates

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From 1983-11-16 to 1983-11-30

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Although this study is guideline and GLP compliant and would normally be assigned a reliability of 1 (reliable without restrictions), this study is used for read-across and therefore has been assigned a reliability of 2 (reliable with restrictions).

Justification for type of information:

The primary component of all substances provide complete coverage of 68334-33-8. 68334-33-8 shares high structural similarity with 61789-80-8, 68783-78-8, 107-64-2, and 112-02-7. As 68334-33-8 is a UVCB its components encapsulate the other substances except for the counter ion (Cl-). In solution, the counter ions will dissociate from the parent structures. Therefore, we are comparing substances of equivalent nature. CAS 107-64-2 represents the C18 boundary of the 61789-80-8. Ignoring the salt component CAS 61789-80-8 is equivalent to CAS 68334-33-8. 68783-78-8 is a worst case of both 68334-33-8 and 61789-80-8 since it is unsaturated and the SP2 carbon-carbon bonds are of higher reactivity and a more likely site of metabolic activation. The primary component of CAS 112-02-7 is a substructure of all the other substances. Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The primary component of all substances provide complete coverage of 68334-33-8. 68334-33-8 shares high structural similarity with 61789-80-8, 68783-78-8, 107-64-2, and 112-02-7. As 68334-33-8 is a UVCB its components encapsulate the other substances except for the counter ion (Cl-). In solution, the counter ions will dissociate from the parent structures. Therefore, we are comparing substances of equivalent nature. CAS 107-64-2 represents the C18 boundary of the 61789-80-8. Ignoring the salt component CAS 61789-80-8 is equivalent to CAS 68334-33-8. 68783-78-8 is a worst case of both 68334-33-8 and 61789-80-8 since it is unsaturated and the SP2 carbon-carbon bonds are of higher reactivity and a more likely site of metabolic activation. The primary component of CAS 112-02-7 is a substructure of all the other substances. Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach.

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 5 000 mg/kg bw

Remarks on result:

other: expressed as Arquat 2HT-75 (a 75% dilution)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Remarks:

but a statement that the report and the study were audited by the Quality Assurance unit is included.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, di-C16-18-alkyldimethyl, chlorides

EC Number:

295-835-2

EC Name:

Quaternary ammonium compounds, di-C16-18-alkyldimethyl, chlorides

Cas Number:

92129-33-4

Molecular formula:

R2N+(CH3)2, Cl- with R is fatty alkyl with chainlengths C16-C18 (even numbered)

IUPAC Name:

N-C16-C18(even numbered)-alkyl-N,N-dimethyl-C16-C18(even numbered)-alkyl-1-aminium chloride

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hacking and Churchill Limited, Huntingdon, UK
- Age at study initiation: four to six weeks of age
- Weight at study initiation: 87 to 108 g
- Fasting period before study: overnight prior and approximately 4 hours after dosing.
- Housing: in groups by sex in metal cages with wire mesh floors
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days prior to the start of the main study

ENVIRONMENTAL CONDITIONS
- Temperature : 23 to 24 °C
- Humidity: 47 %
- Air changes (per hr): 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12hr/12hr

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: the test item was prepared as a 50 % w/v suspension in 1% methyl cellulose.
- Amount of vehicle (if gavage): dose volumes were calculated from the body weights of the rats and the selected dose volume did not exceed 10 mlLkg body weight.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 rats/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at frequent intervals on day 1 (day of dosing) then at least twice a day, weighing at 1, 8 and 15 days after exposure
- Necropsy of survivors performed: yes

Statistics:

none

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 5 000 mg/kg bw

Remarks on result:

other: expressed as Arquat 2HT-75 (a 75% dilution)

Mortality:

No deaths were observed during the study.

Clinical signs:

other: - In all animals, piloerection, pallor of the extremities and hunched posture were observed from day 1 to day 4 (recovery complete by day 4). - In all females and 2 males, abnormal gait was observed from day 1 to day 4 (recovery complete by day 4).

Gross pathology:

No abnormalities were detected at autopsy.

Any other information on results incl. tables

 

Acute oral toxicity, limit test, cumulative mortality
Day	Dose (mg/kg bw)	Sex	Dose (mg/kg bw)	Sex
	5000	F	5000	M
	Cumulative mortality		Cumulative mortality
1	0/5		0/5
2	0/5		0/5
3	0/5		0/5
4	0/5		0/5
5	0/5		0/5
6	0/5		0/5
7	0/5		0/5
8	0/5		0/5
9	0/5		0/5
10	0/5		0/5
11	0/5		0/5
12	0/5		0/5
13	0/5		0/5
14	0/5		0/5
15	0/5		0/5

 

Acute oral toxicity, limit test, 5000 mg/kg bw
Sex	Mean body weight in grams
	Day 1	Day 8	Day 15
M	105	178	255
M	103	186	272
M	95	177	255
M	93	163	239
M	107	188	250
F	90	142	174
F	87	142	189
F	102	161	203
F	107	161	200
F	108	169	206

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on this study, the acute oral LD0 of the 75% dilution of the substance is equal to or greater than 5000 mg/kg bw.

Executive summary:

The objective of this study was to evaluate the toxicity of a 75% dilution of the test item (DHTDMAC 75% active in isopropanol/water) following a single oral administration in rats according to OECD guideline 401. A statement that the report and the study were audited by the Quality Assurance Unit of the testing laboratory was provided. The test material was prepared in 1% methylcellulose suspension and was administered by gavage under a dosage-volume of 10 mL/kg bw to 2 groups of 5 male and 5 female rats. Based on a preliminary study indicating no deaths in 2 males and 2 female rats at 5000 mg/kg bw, the main experiment was performed at the limit dose level of 5000 mg/kg bw. Clinical signs, mortality and body weight were checked for a period of 14 days following the single administration of the test item. All animals were subjected to necropsy.

At the dose level of 5000 mg/kg, no mortality and no effects on body weight gain were observed.

Piloerection, pallor of the extremities and hunched posture were observed in all animals from day 1. Abnormal gait was also recorded in 2 out of 5 males and 5 out of 5 females. Recovery was complete by day 4. At necropsy, there were no apparent abnormalities. Under these experimental conditions, the oral LD0 of the 75% dilution of the substance is equal to or greater than 5000 mg/kg bw.