Reaction mass of sodium sulphate and disodium dodecanedioate and Dodecanoic acid, 12-amino-, sodium salt (1:1)

Endpoint summary

Description of key information

-Acute oral : The test item is not harmful or toxic by oral route with a LD50> 2000 mg/kg bw. A guideline study (OECD 423) is available in rat.
-Acute dermal : The test item is not harmful or toxic by dermal route with a LD50> 2000 mg/kg bw. A guideline study (OECD 402) is available in rat.
-Acute inhalation: No data is available (Waiving).

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

Study period:

07 July 2010 - ............................

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Compliant to GLP and testing guideline; adequate coherence between data, comments and conclusions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

the animals were not housed individually.

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

idem above

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 198 ± 8 g
- Fasting period before study: 18 hours
- Housing: polycarbonate cages with stainless steel lid, not individually
- Diet (e.g. ad libitum): free access to SSNIFF R/M-H pelleted diet
- Water (e.g. ad libitum): free access to bottles containing tap water (filtered with a 0.22 m filter)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): 12 cycles/hour
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00-19:00)

IN-LIFE DATES: From: 09 July 2010 To: 12 August 2010

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

purified

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: the test item was soluble in purified water at 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As no information on the toxic potential of the test item was available, for animal welfare reasons,
the starting dose-level of 300 mg/kg was chosen.

Doses:

300 and 2000 mg/kg.

No. of animals per sex per dose:

3 females per treatment step (300, 2000 and 2000 mg/kg).

Control animals:

no

Details on study design:

- Duration of observation period following administration: a period of up to 14 days
- Frequency of observations and weighing: each animal was observed after dosing at least once during the first 30 minutes, periodically during the
first 24 hours for detection of possible treatment-related clinical signs and then at least once a day for 14 day.
Type, time of onset and duration of clinical signs were recorded for each animal individually.
The body weight of each animal was recorded just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the study.

Clinical signs:

other: At the dose-level of 300 mg/kg (three females), no clinical signs were observed. At the dose-level of 2000 mg/kg (three females then confirmation on three other females), ptyalism and loud breathing were noted in one animal within one hour of treatment,

Gross pathology:

Macroscopic post-mortem examination of the main organs of the animals revealed no apparent abnormalities.

Other findings:

None.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: Regulation EC no.1272/2008

Conclusions:

The oral LD50 of the test item, Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate (batch No. T710/712), was higher than 2000 mg/kg in rats.

Executive summary:

The objective of this study was to evaluate the toxicity of the test item, Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate, following a single oral administration in rats according to OECD 423 and Commission Regulation (EC) (No. 440/2008, B.1tris, 30 May 2008) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

Methods

The test item, Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate, was administered by oral route (gavage) to groups of three fasted female Sprague-Dawley rats at dose-levels of 300 and 2000 mg/kg under a dosage-volume of 10 mL/kg. The test item was prepared in purified water.

Each animal was observed at least once a day for mortality and clinical signs for a period of up to 14 days following the single administration. Body weight was recorded on day 1 and then on days 8 and 15. On completion of the observation period, the animals were sacrificed then subjected to a macroscopic post-mortem examination.

At necropsy, no apparent abnormalities were observed in any animal.

Results

No mortality was observed during the study. At the dose-level of 300 mg/kg (three females), no clinical signs were observed. When compared to CIT historical control data, the body weight gain of the animals was not affected by treatment with the test item. At the dose-level of 2000 mg/kg (three females then confirmation on three other females), ptyalism and loud breathing were noted in one animal within one hour of treatment, and piloerection was observed in another one 20 minutes after treatment. When compared to CIT historical control data, a lower body weight gain was noted in 1/6 females (vs. 41 ±in control data base) between day 1 and day 8. The body weight gain of this animal returned to normal thereafter.

Conclusion

The oral LD50of the test item, Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate (batch No. T710/712), was higher than 2000 mg/kg in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

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:

07 July 2010 - September 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Compliant to GLP and testing guideline (the deviation was not considered to have compromised the validity of the study and results); adequate coherence between data, comments and conclusions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

all males had a body weight higher than 320 g (up to 355 g)

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

idem above

GLP compliance:

yes (incl. QA statement)

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: Breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: a mean body weight ± standard deviation of 353 ± 2 g for the males and 218 ± 9 g for the females
- Fasting period before study: none
- Housing: polycarbonate cages with stainless steel lid
- Diet (e.g. ad libitum): free access to SSNIFF R/M-H pelleted diet
- Water (e.g. ad libitum):f ree access to bottles containing tap water (filtered with a 0.22 µm filter)
- Acclimation period: at least 5 days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

IN-LIFE DATES: From: 12 July 2010 To: 27 July 2010.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 5 cm x 7 cm for males and 5 cm x 6 cm for females
- % coverage: approximately 10% of the total body surface area of the animals
- Type of wrap if used: a hydrophilic gauze pad held in place with an aerated hypoallergenic.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): on removal of the dressing, any residual test item was removed using a moistened cotton pad
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (1.69 mL/kg)

Duration of exposure:

24 hours.

Doses:

2000 mg/kg.

No. of animals per sex per dose:

5 animals per sex and per dose.

Control animals:

other: historical control data

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: each animal was observed frequently during the hours following administration, for detection of possible treatment-related clinical signs then at least once a day for 14 day
- Necropsy of survivors performed: yes.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None.

Clinical signs:

other: Exophthalmos, then corneal opacity, was observed on the left eye of one animal only from day 3 and day 12 to the end of the observation period, respectively. Erythema was noted on two males on days 2 and 3. Erythema was also noted on three, four and five

Gross pathology:

Macroscopic post-mortem examination of the main organs of the animals revealed no apparent abnormalities.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: Regulation EC no. 1272/2008

Conclusions:

The dermal LD50 of the test item Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate
(batch No. T710/712) was higher than 2000 mg/kg in rats.

Executive summary:

The objective of this study was to evaluate the toxicity of the test item, Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate (batch No. T710/712), following a single dermal application to rats according to OECD (No. 402, 24th February 1987) and Commission Regulation (EC) (No. 440/2008, Part B.3, 30 May 2008) guidelines .

The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

 

Methods

The test item, Reaction mass of sodium sulfate, sodium amino-12-dodecanoate, was applied undiluted for 24 hours to the skin of five male and five female Sprague‑Dawley rats at the dose‑level of 2000 mg/kg, then the test site was covered by a semi‑occlusive dressing.

Each animal was observed at least once a day for mortality and clinical signs for a period of up to 14 days following the single administration. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed then subjected to a macroscopic post-mortem examination.

 

Results

No deaths were observed during the study. Exophthalmos, then corneal opacity, was observed on the left eye of one animal only from day 3 and day 12, respectively, to the end of the observation period.

Erythema was noted on two males on days 2 and 3. Erythema was also noted on three, four and five females on days 2, 3 and 4, respectively. It persisted on these females until day 10 (one female), day 14 (one female) and the end of the observation period (three other females).

A brown discoloration of the skin, was observed in 9/10 animals until day 3, and until day 8 in 1/10 animals. It masked the evaluation of local reactions in one of them until day 3. Scabs were observed from day 4 until the end of the observation period in one female only.

When compared to CIT historical control data, a lower body weight gain was noted between day 1 and day 8 in all males (from 25 to vs. 47 ± in control data base) and 1/5 females (11 g vs. 25 ± in control data base). The body weight gain of these animals returned to normal thereafter.

 

No apparent abnormalities were observed at necropsy in any animal.

Conclusion

Under the experimental conditions of this study, the dermal LD₅₀of the test item Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate (batch No. T710/712) was higher than 2000 mg/kg in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute oral (OECD 423, 2010):

The test item, Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate, was administered by oral route (gavage) to groups of three fasted female Sprague-Dawley rats at dose-levels of 300 and 2000 mg/kg under a dosage-volume of 10 mL/kg. The test item was preparedin purified water.

No mortality was observed during the study. At the dose-level of 300 mg/kg (three females), no clinical signs were observed. When compared to CIT historical control data, the body weight gain of the animals was not affected by treatment with the test item.At the dose-level of 2000 mg/kg (three females then confirmation on three other females), ptyalism and loud breathing were noted in one animal within one hour of treatment, and piloerection was observed in another one 20 minutes after treatment. When compared to CIT historical control data, a lower body weight gain was noted in 1/6 females (vs.41 ±in control data base) between day 1 and day 8. The body weight gain of this animal returned to normal thereafter.

At necropsy, no apparent abnormalities were observed in any animal. The oral LD50 of the test item, Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate was higher than 2000 mg/kg in rats.

Acute dermal (OECD 402, 2010):

The test item, Reaction mass of sodium sulfate, sodium amino-12-dodecanoate, was applied undiluted for 24 hours to the skin of five male and five female Sprague‑Dawley rats at the dose‑level of 2000 mg/kg, then the test site was covered by a semi‑occlusive dressing.Each animal was observed at least once a day for mortality and clinical signs for a period of up to 14 days following the single administration. Body weight was recorded on day 1 and then on days 8 and 15.On completion of the observation period, the animals were sacrificed then subjected to a macroscopic post-mortem examination.

No deaths were observed during the study. Exophthalmos, then corneal opacity, was observed on the left eye of one animal only from day 3 and day 12, respectively, to the end of the observation period.

Erythema was noted on two males on days 2 and 3. Erythema was also noted on three, four and five females on days 2, 3 and 4, respectively. It persisted on these females until day 10 (one female), day 14 (one female) and the end of the observation period (three other females).

A brown discoloration of the skin, was observed in 9/10 animals until day 3, and until day 8 in 1/10 animals. It masked the evaluation of local reactions in one of them until day 3. Scabs were observed from day 4 until the end of the observation period in one female only.

When compared to CIT historical control data, a lower body weight gain was noted between day 1 and day 8 in all males (from 25 tovs. 47 ± in control data base) and 1/5 females (11 g vs. 25 ± in control data base). The body weight gain of these animals returned to normal thereafter.

No apparent abnormalities were observed at necropsy in any animal.

Under the experimental conditions of this study, the dermal LD₅₀of the test item was higher than 2000 mg/kg in rats.

Justification for classification or non-classification

Acute oral:

According to EU Directive 67/584/EEC and EU regulation (EC) No 1272/2008 (CLP), the Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate is not classified for acute oral toxicity.

Justification : LD 50> 2000 mg/kg bw

Acute dermal:

According to EU Directive 67/584/EEC and EU regulation (EC) No 1272/2008 (CLP), the Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate is not classified for acute dermal toxicity.

Justification : LD 0> 2000 mg/kg bw

Acute inhalation:

There are no data therefore, the Reaction mass of sodium sulfate, sodium amino-12-dodecanoate and sodium dodecanoedioate is not classified for acute inhalation toxicity.