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

Endpoint summary

Description of key information

Oral: OECD 401; rat LD50 >2000 mg/kg. Reliability = 2 (read-across substance)

Inhalation: rat; LC50 >180 mg/L. Reliability = 2 (read-across substance)

Dermal: OECD 402; rat LD50 >2000 mg/kg. Reliability = 2 (read-across substance)

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 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.

Reason / purpose for cross-reference:

read-across: supporting information

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

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

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

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.

 

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

The study predates respective OECD guidelines and Good Laboratory Practices but was conducted according to regulations for the Enforcement of the Federal Hazardous Substa nces Act (USA). The main limitations of the study are the exposure duration which was restricted to one hour and the lack of determination of the actual exposure concentrations. There were no details on the exposure conditions and in particular on the particle-size distribution of the generated aerosol.

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: supporting information

Qualifier:

according to guideline

Guideline:

other: Revised, Federal Register, September 17, 1964

Principles of method if other than guideline:

Rats were exposed (whole-body) to the test substance suspended in distilled water for 1 hour at a concentration of 180 mg/L. Observations of the appearance and behaviour of the animals were made continuously during the exposure period, and at frequent intervals thereafter for a total of 14 days. At the end of the observation period the rats were weighed, sacrificed and gross necropsies were performed.

GLP compliance:

no

Test type:

other: standard acute method

Species:

rat

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 227 - 276 g
- Housing: by groups in wire mesh cages
- Diet: ad libitum (except during exposure)
- Water : ad libitum (except during exposure)
No other data available.

ENVIRONMENTAL CONDITIONS
No data available.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: water

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: chamber consisted of a glass jar fitted with a plexiglass lid.
- Exposure chamber volume: 29 cm in diameter and 30 cm deep.
- Source and rate of air: The lid contained air intake and exit tubes positioned at the top and bottom of the chamber, respectively. air flow was 10 L/min.
- System of generating particulates/aerosols: The sample was introduced into the chamber atmosphere by using a Preval pack and a series of one or two second sprays approximately every 30 seconds.
No other data available.

TEST ATMOSPHERE
- No analytical measures were performed.
- Particle size distribution and Mass median aerodynamic diameter were not determined.

VEHICLE
- Composition of vehicle : water
- Concentration of test material in vehicle : A suspension of the test substance in distilled water was prepared by adding 1 part test substance to 29 parts water.
No other data available.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

60 min

Concentrations:

180 mg/L

No. of animals per sex per dose:

10 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: continuously during the exposure period, and at frequent intervals thereafter. Body weights were recorded prior to dosing and at the end of the observation period.
- Necropsy of survivors performed: yes

Statistics:

None

Preliminary study:

Not performed

Sex:

male

Dose descriptor:

LC50

Effect level:

> 180 mg/L air (nominal)

Exp. duration:

60 min

Mortality:

No mortalities occurred during the study.

Clinical signs:

other: - During the exposure period: the rats exhibited "excited" activity upon initiation. The majority of rats exhibited preening, excessive masticatory movements, excessive salivation stains, damp hair coats, lacrimation and serosanguinous stains around the n

Body weight:

The rats showed an average body weight gain of 26 g over the course of the study, which was considered to be normal for rats of this age strain and sex.

Gross pathology:

No abnormalities detected.

Interpretation of results:

GHS criteria not met

Conclusions:

The 1-hour LC50 was found to exceed 180 mg/l. No mortalities occurred and the symptomatology restricted to the day of exposure did not indicate a toxic potential by inhalation.

Executive summary:

The acute inhalation toxicity of the test item (DHTDMAC, 75% active in isopropanol/water) was assessed in male albino rats using a technique from the US Federal Hazardous Substances Regulations specified in the Revised, Federal Register, september 17, 1964. The study predates GLP requirements. A group of ten rats were exposed whole-body to the test item in an inhalation chamber for 1 hour. The nominal concentration of the test item in the chamber atmosphere was calculated to be 180 mg/L of mist. At the end of the exposure period, the animals were removed from the chamber. The animals were observed continuously for appearance and behavior during the exposure period and at regular intervals thereafter for a total of 14 days. Rats were subjected to gross necropsy at the end of the study.

No mortalities were recorded at any time. Clinical signs were only present on the day of exposure and included, excess salivation, serosanguineous stains around the nose, laboured respiration and damp/wet coats. For the remainder of the study, all rats exhibited normal behaviour and appearance. Necropsy revealed no significant gross pathological alterations. The acute LC50 was determined to be greater than180 mg/L after a 1-hour exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

180 000 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

From 1988-03-16 to 1988-03-0-30

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to 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.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

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: Charles River France
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: males: 281 ± 5 g; females: 221 ± 6 g
- Fasting period before study: no
- Housing: polypropylene cages (one animal per cage)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): 12 hours periodically

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 7 cm
- % coverage: approximately 10% of body surface
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): n.a.
- Constant volume or concentration used: n.a.
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): water
- Concentration (if solution): n.a.
- Lot/batch no. (if required): n.a.
- Purity: n.a.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight (limit dose)

No. of animals per sex per dose:

5 male; 5 female

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality througout study period.

Clinical signs:

other: No clinical signs throughout study period.

Gross pathology:

No abnormalities

Other findings:

- Organ weights: no data
- Histopathology: not performed
- Potential target organs: no target identified
- Other observations: none

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test material was greater 2000 mg/kg body weight in rats.

Executive summary:

The acute dermal toxicity of the test material (dihydrogenated tallowalkyldimethyl ammonium chloride, purity approximately 97%) was investigated in rats according to OECD Test Guideline 402 in compliance with the principles of GLP. The test substance was applied as an aqueous suspension to the shaved skin of 5 male and 5 female animals at a dose level of 2000 mg/kg body weight (limit dose) under occlusive conditions. Mortality, general behaviour, clinical signs and body weight development were recorded daily for an observation period of 14 days. A necropsy was performed on each animal sacrificed at the end of the study.

There was no mortality throughout the study period at the dose level of 2000 mg/kg body weight. General behaviour and bodyweight of the animals were not influenced by the treatment. Clinical

signs of significance were not observed. Skin dryness was noted after the removal of the dressing up to day 6 in all animals. Additional signs of skin irritation were not observed. The macroscopic examination of the main organs did not reveal abnormalities in any of the animals sacrificed at the end of the observation period. Based on the study results, the median lethal dose (LD50) of the test material when administered dermally to rats is greater than 2000 mg/kg body weight. Additionally, at this dose level the test material did not induce any signs of toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

No acute oral, dermal, or inhalation studies with the test substance are available. Therefore, a study with DHTDMAC (CAS 61789-80-8) was used as read across to fulfil the data gap for the test substance. 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.

The acute dermal toxicity of DHTDMAC (dihydrogenated tallowalkyldimethyl ammonium chloride, purity approximately 97%) was investigated in rats according to OECD Test Guideline 402 in compliance with the principles of GLP. The test substance was applied as an aqueous suspension to the shaved skin of 5 male and 5 female animals at a dose level of 2000 mg/kg body weight (limit dose) under occlusive conditions. Mortality, general behaviour, clinical signs and body weight development were recorded daily for an observation period of 14 days. A necropsy was performed on each animal sacrificed at the end of the study. There was no mortality throughout the study period at the dose level of 2000 mg/kg body weight. General behaviour and bodyweight of the animals were not influenced by the treatment. Clinical signs of significance were not observed. Skin dryness was noted after the removal of the dressing up to day 6 in all animals. Additional signs of skin irritation were not observed. The macroscopic examination of the main organs did not reveal abnormalities in any of the animals sacrificed at the end of the observation period. Based on the study results, the median lethal dose (LD50) of the test material when administered dermally to rats is greater than 2000 mg/kg body weight. Additionally, at this dose level the test material did not induce any signs of toxicity.

 

The acute inhalation toxicity with dihydrogenatedtallowalkyldimethylammonium chloride (DHTDMAC, 70% active in isopropanol/water) was assessed in male albino rats using a method recommended by the US Federal Hazardous Substances Regulations specified in the Revised, Federal Register. A group of ten rats were exposed whole-body to the test item in an inhalation chamber for 1 hour. The nominal concentration of the test item in the chamber atmosphere was calculated to be 180 mg/L of mist. The animals were observed continuously for appearance and behaviour during the exposure period and at regular intervals thereafter for a total of 14 days. Rats were subjected to gross necropsy at the end of the study. No mortalities were recorded at any time. Clinical signs were only present on the day of exposure and included, excess salivation, serosanguineous stains around the nose, laboured respiration and damp/wet coats. For the remainder of the study, all rats exhibited normal behaviour and appearance. Necropsy revealed no significant gross pathological alterations. The acute LC50 of the test material was determined to be greater than180 mg/L after 1 hour of exposure.

Justification for classification or non-classification

Based on the oral and dermal LD50 in rats of >5000 mg/kg and >2000 mg/kg, respectively, as well as an inhalation LC50 of >180 mg/L in read-across substances, no classification is required for acute oral, dermal, or inhalation endpoints according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.