Diammonium 2,2'-dithiodiacetate

Endpoint summary

Description of key information

Classification as acute tox. 4 based on the determined oral LD50 between 300 and 500 mg/kg bw. Classification criteria for dermal route not met, LD0>2000 mg/kg bw.

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:

1999 - 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

Dir. 96/54/EC

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals: Sprague Dawley CD (Crl: (SD) IGS BR)
Source: Ch River (UK) Ltd, Margate Kent
Acclimatization period: 15-21 days
Weight range at study initiation:209-220 g (m), 202 - 236 g (f)
Acclimatisation at least 5 days
Fasting:overnight before dosing and 3-4 hours after dosing

Husbandry:
Housing: collective housing up to a maximum of 3 animals by sex per cage (Polypropylene)
Illumination: artificial lighting from 7.00 a.m.-7.00 p.m.
Temperature: 22±3 °C
Relative humidity: 30-70%
15 air changes / h

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The acute oral toxicity of "Diammonium dithiodiglycolate 48 %" was investigated according to a stepwise procedure in Sprague-Dawley rats acc. OECD 423

Doses:

200, 500, 2000 mg/kg body weight

No. of animals per sex per dose:

200mg/ kg : 3/3
500 mg/kg : 3 f
2000 mg/kg: 3 f

Control animals:

no

Details on study design:

Clinical observations were conducted at regular intervals during the 14-day observation period.
Gross pathological examinations were performed immediately on animals found dead and at termination on day 14 on surviving animals.
Body weights were measured at days 0, 7 and 14.

Statistics:

n.a.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - < 500 mg/kg bw

Based on:

act. ingr.

Mortality:

Two animals treated with 2000 mg/kg and 500 mg/kg were found dead during the day of dosing. One anaimal treated with 2000 mg/ kg was killed in extremis during the day of dosing.
No deaths occured on 200 mg/kg dosing.

Clinical signs:

other: Individual observations are attached in the result tables in "background information" Common signs of toxicity noted at dose levels of 2000 mg/kg were hunched posture, decreased respiratory rate, and laboured respiration with incidents of ataxia, hypother

Gross pathology:

Individual necropsy findings are attached in the result tables in "background information" table 10 and 13

Abnormalities noted at necropsy of animals that died or the animal that was killed in extremis during the study were haemorrhagic or abnormally red lungs, dark liver, dark kidneys, haemorrhagic gastric mucosa and haemorrhagic small intestine. No abnormalitiees were noted at necropsy of animals that were killed at the end of the study.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of the test material diammonium dithiodiglycolate 48% w/w in water in Sprague-Dawley rats was estimated to be in the range of 300 to 500 mg/kg body weight.
Mortalities were noted at 500 and 2000 mg/kg bodyweight.

The test material was classiefied as Acute tox. 4 according to the GHS criteria.

Executive summary:

The acute oral toxicity of the test material diammonium dithiodiglycolate 48% in water (diammonium 2,2'-dithiodiacetate) was evaluated accing OECD 423 (EU B.1) gueidelines.

All animals trates with 2000 mg/kg bodyweight died in the first day of observation. All animals treated with 200 mg/kg bodyweight survived with no clinical signs and normal gain of body weight.

2 Animals treated with 500 mG/kg bodyweight died. The surviving animal recovered three days after dosing with no clinical signs at the end of the study.

Stating a LD50 value of 300 to 500 mg/kg bodyweight the test material was classified as acute tox. 4

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 300 - < 500 mg/kg bw

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)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EC 92/69/EEC (1992-07-31)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

ten animals (5 male, 5 female) age appr. 9 weeks mean body weight 308+-8 (male), 226+-11 (female)
Acclimation 5 days before study start
Environmental condition:
- 22+-2 °C
- 30 - 70% rel. humidity
- 12/12 h light dark cycle
- ventilation: 12 cycles/h of filtered non recycled air
records of conditiones were checked daily. Instrument calibration at regular intervals.

During acclimation animals were house one to seven animals of same sex in polycarbonate cages with stainless steel lid.
During treatment period animals were housed individually in PC cages of 35.5x23.5x19.3 dimension, on autoclaved sawdust (SICSA, Alfortville France)
Food and Water: All animals had free access to pelleted diet (A04C, SAFE, Villemoisson, Epinay-sur-Orge, France) and Water filtered by FG Millipore membrane 0.22µ ad libitum.

In Life date: 12 to 26 of march 2003

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: a dorsal area of the skin (approximately 5 cm x 6 cm for the females and 5 cm x 7 cm for the males)
- % coverage: approximately 10%
- Type of wrap if used: hydrophilic gauze pad held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.6 mL/kg
- Constant volume or concentration used: no

Duration of exposure:

24 h

Doses:

2000 mg/kg of the 48% solution (960 mg/kg active ingredient)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The animals were observed frequently during the hours following administration of the test itemfor detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15.
From day 2, any local cutaneous reaction was recorded.
The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
The body weight gain of the treated animals was compared to that of CIT control animals with a similar initial body weight.
- Necropsy of survivors performed: yes
- Other examinations performed: Macroscopic necropsy examination:All study animals were subjected to a macroscopic examination as soon as possible after death. After opening the thoracic and abdominal cavities, a macroscopic examination of the main morgans (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed. Preservation of tissues: No organ samples were taken.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 960 mg/kg bw

No clinical signs and no deaths were observed during the study.

A reduced body weight gain was observer in 2 mals and 2 females in da 1 to 8 and one male in day 8 to 15. The other anaimals were not affected in comparison to historical control animals.

No cutaneous reactions were observed.

No apparent abnormalities were observed at necroscopy of any animals.

The LD0 is higher than 2000 mg/kg of a 48% aqueous solution of the test material (equivalent to 960 mg/kg of active ingredient)

Interpretation of results:

GHS criteria not met

Conclusions:

No effects could be observed up to the highest test concentration (2000 mg/kg). Therefore, the LD0 is determined to be >2000 mg/kg. According to the classification criteria (Dir 67/548/EC)GHS criteria the test item should not be classified.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD0

Value:

> 2 000 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
OECD TG study

Justification for selection of acute toxicity – inhalation endpoint
With reference to Annex VIII, Column 2, 8.5.2 of Regulation (EC) No.1907/2006, taking into account the very low vapour pressure of diammonium dithiodiglycolate, exposure of humans via inhalation is unlikely to occur and not a relevant route of exposure. Furthermore, diammonium dithiodiglycolate is not applied as spray or mist so that exposure to respirable aerosols can also be excluded.

Justification for selection of acute toxicity – dermal endpoint
OECD TG study

Justification for classification or non-classification

 

The substance DADTDG should be classified as acute tox. 4 based on an oral LD50 value of 300 to 500 mg/kg bw.