Reaction mass of bis(N-decyl-N,N-dimethyldecan-1-aminium) carbonate and N-decyl-N,N-dimethyldecan-1-aminium hydrogen carbonate

Endpoint summary

Description of key information

Acute oral toxicity 
A study was carried out according to OECD Guideline 401 (Acute Oral Toxicity) and US FIFRA (40 CFR). The study revealed a LD50 of 245 mg a.i./kg bw (135 – 443 mg a.i./kg bw) and a NOEL of 25 mg a.i./kg bw.
Acute inhalation toxicity
According to column 2 of REACH Regulation (EC) No 1907/2006 Annex VIII, section 8.5 testing by the inhalation route was waived, as an acute oral toxicity study and an acute dermal toxicity study are available. Only two acute dose toxicity studies are required, with test item administration via the most appropriate routes.
Acute dermal toxicity 
A study was carried out according to EU Method B.3 and OECD Guideline 402 (Acute Dermal Toxicity). Due to the severity of the dermal reactions, tested animals were killed in extremis one day after dosing. There were no signs of systemic toxicity. Signs of dermal irritation were indicative of dermal corrosion. No abnormalities were noted at necropsy. Therefore, the acute dermal median lethal dose may be considered to be greater than 2000 mg/kg bw although there is insufficient data available to confirm this finding. 

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to international guidelines.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

other: FIFRA (40 CFR)

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
- Age at study initiation: Young adults
- Weight at study initiation:
Male: 242 – 300 g
Female: 189 – 254 g

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5 %

Doses:

Dose range finding: 100, 250, 500 mg a.i./kg
Definitive test: 25, 50, 100, 200, 400, 800 mg a.i./kg

No. of animals per sex per dose:

Dose range finding: 2/sex/group
Definitive test: 5/sex/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 0, 7 and 14
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs

In addition the post-exposure observation period was extended to 21 days for those rats exposed to 200 and 400 mg/kg of Carboquat due to the toxic effects observed on day 14.

Preliminary study:

For results see table 1a below. Definitive test doses were based on the results obtained in the preliminary test.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

245 mg/kg bw

Based on:

act. ingr.

95% CL:

135 - 443

Sex:

male/female

Dose descriptor:

LD0

Effect level:

25 mg/kg bw

Based on:

act. ingr.

Mortality:

For results see table 1b below.

Clinical signs:

other: A variety of clinical signs were observed for males and females in the 800 mg a.i./kg bw treatment group which died as a result of treatment. These signs were generally indicative of increased secretions, changes in the appearance of the fur and posture,

Gross pathology:

Findings in the animals that died during the observation period were those generally seen in agonal animals with additional observation generally seen in response to the oral administration of an irritating material. All animals at the 400 mg a.i./kg bw dose level and one animal at the 200 mg a.i./kg bw dose level which survived the observation period exhibited tissue adhesions in the peritoneal cavity in the area of the stomach. Furthermore, all animals which survived the observation period at the 100 mg a.i./kg bw dose level exhibited livers and spleens which appeared pitted. In all other animals which survived the observation period there were no gross pathological findings.

Table 1a: Group incidence of mortality - Dose range finding screen:

Dose (mg a.i./kg)	Mortality (No. dead/No. dosed)
	Male	Female
500	2/2	2/2
250	2/2	2/2
100	0/2	0/2

Table 1b: Group incidence of mortality - Definitive test

Dose (mg a.i./kg)	Mortality (No. dead/No. dosed)
	Male	Female
800	5/5	5/5
400	2/5	4/5
200	2/5	3/5
100	1/5	0/5
50	0/5	1/5
25	0/5	0/5

 

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity study revealed a LD50 of 245 mg a.i./kg bw (135 – 443 mg a.i./kg bw) and a NOEL of 25 mg a.i./kg bw.

Executive summary:

A study was carried out according to OECD Guideline 401 (Acute Oral Toxicity) and US FIFRA (40 CFR). The study was performed on male and female Sprague Dawley rats at dose levels of 800, 400, 200, 100, 50 and 25 mg a.i./kg bw. All levels were dosed with a 5 % w/w aqueous formulation of DDACarbonate. Rats were observed for 14 days post-dosing. A gross necropsy was performed on any animal that died and at the end of the observation period, all animals were sacrificed for gross necropsy. The acute oral toxicity study revealed a LD50 of 245 mg a.i./kg bw (135 – 443 mg a.i./kg bw) and a NOEL of 25 mg a.i./kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

245 mg/kg bw

Quality of whole database:

High quality database.

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

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Remarks:

Safepharm Laboratories Ltd

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:

On receipt the animals were randomly allocated to cages. The female was nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by a number written on a cage card. At the start of the study the animals weighed at least 200g, and were eight to twelve weeks of age.
The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually. Free access to mains drinking water and food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

IN-LIFE DATES: 09 June 2004 and 10 June 2004

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The study was performed to assess the dermal toxicity of the test material in the rat. Two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy at termination of the study.

TEST SITE
- Area of exposure: back and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: surgical gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material
- Time after start of exposure: 24-hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.09 mL/kg

Duration of exposure:

24 hours

Doses:

Limit test 2000 mg/kg bw

No. of animals per sex per dose:

1 male and 1 female animal

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2, 4 hours and one day after dosing.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Due to the severity of the dermal reactions noted in the initial two animals, resulting in these animals being killed in extremis one day after dosing, no further animals were treated.

Mortality:

Due to the severity of the dermal reactions, both animals were killed in extremis one day after dosing.

Clinical signs:

other: Signs of dermal irritation noted were brown/green coloured dermal necrosis (attributed a Draize score of 4 for erythema due to injuries in depth), surrounded by a thin margin of blanching and moderate oedema. Well-defined erythema surrounding other dermal

Gross pathology:

No abnormalities detected.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The animals showed no signs of toxicity but were killed in extremis due to the severity of the dermal reactions. The acute dermal median lethal dose may be considered to be greater than 2000 mg/kg bw although there is insufficient data available to confirm this finding.

Executive summary:

A study was carried out according to EU Method B.3 and OECD Guideline 402 (Acute Dermal Toxicity). The study was performed to assess the dermal toxicity of the test material in the rat. Two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy at termination of the study.

Due to the severity of the dermal reactions, both animals were killed in extremis one day after dosing. There were no signs of systemic toxicity. Signs of dermal irritation were indicative of dermal corrosion. No abnormalities were noted at necropsy. The acute dermal median lethal dose may be considered to be greater than 2000 mg/kg bw although there is insufficient data available to confirm this finding.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

High quality database.

Additional information

Justification for selection of acute toxicity – oral endpoint
GLP study according to international guidelines.

Justification for selection of acute toxicity – dermal endpoint
GLP study according to international guidelines.

Justification for classification or non-classification

Based on the information available the substance is classified and labeled as Acute Toxicity Cat. 4, H302: Harmful if swallowed according to Regulation (EC) No 1272/2008 (CLP) and Xn, R21: Harmful in contact with skin and R22: Harmful if swallowed according to Directive 67/548/EEC (DSD).