Phosphorodithioic acid, O,O-di-dodecyl-esters, zinc salts, neutral and basic

Endpoint summary

Description of key information

Oral LD50 > 2000 mg/kg bw

RA from CAS 4259-15-8

Dermal LD50 > 5000 mg/kg bw

RA from CAS 4259-15-8

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(non-GLP)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 232-296 g
- Housing: Housed individually in wire bottom cages
- Diet: ad libitum except overnight prior to dosing
- Water: ad libitum except overnight prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2200 mg/kg, 3300 mg/kg, 5000 mg/kg, 7500 mg/kg

No. of animals per sex per dose:

10 male

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology including: thymus, heart, lungs, liver, kidneys, adrenal glands, spleen, gonads, gastro-intestinal tract, lymph nodes, pancreas, salivary glands, bladder, body fat, skeletal muscle, teeth, eyes and skin.

Statistics:

Berkson, J. Biometrika, 44:411-435, 1957

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

3 100 mg/kg bw

95% CL:

> 1 800 - < 5 100

Mortality:

7500 mg/kg: 10/10 rats died 1-2 days after exposure
5000 mg/kg: 9/10 rats died between 1-9 days after exposure
3300 mg/kg: 6/10 rats died 1-2 days after exposure
2200 mg/kg: 2/10 rats died between 1-8 days after exposure

Clinical signs:

Depresson, diarrhea, reduced food intake

Gross pathology:

Survivors had less than normal amounts of body fat. No other changes were observed.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008

Conclusions:

CLP: not classified

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

03/02/1983 - 4/13/1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(purity of the test material not given)

Qualifier:

according to guideline

Guideline:

other: Section 1500.3 – Federal Hazardous Substance Act Regulations – 16 CFR.

Deviations:

no

GLP compliance:

yes

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:

TEST ANIMALS
- Age at study initiation: approx. 7 weeks of age
- Weight at study initiation: average weight between 200~300 g.
- Fasting period before study: Feed was withheld overnight prior to dosing.
- Housing: the animals were housed and maintained in accordance with standards set forth in the Guide for Care and Use of Laboratory Animals (DHEW publication No. 80-23). 5 rats/cage by sex.
- Diet: Wayne Lab-Blox, provided ad libitum.
- Water: tap water available ad libitum.
- Acclimation period: acclimated to the laboratory for an appropriate time prior to dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3 - 22.8
- Humidity (%): 45 - 55
- Air changes: controlled environment, but no air change information provided.
- Photoperiod: 12 h light/dark cycle

IN-LIFE DATES: From: 03/02/1983 To: 04/13/1983.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000 and 5000 mg/kg bw

No. of animals per sex per dose:

5 /sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed frequently on the day of dosage and twice daily thereafter (morning and afternoon). Individual weights were recorded on the day of dosage, weekly thereafter and prior to sacrifice.
- Necropsy of survivors performed: gross necropsies were performed on all animals that either died during the 14 day observation period or on surviving animals that were sacrificed at the conclusion of the 14 day observation period.

Statistics:

No data available.

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 - < 5 000 mg/kg bw

Mortality:

5000 mg/kg
Male: Number of animals: 5; Number of deaths: 5
Female: Number of animals: 5; Number of deaths: 5

2000 mg/kg
Male: Number of animals: 5; Number of deaths: 0
Female: Number of animals: 5; Number of deaths: 1

Clinical signs:

All animals died in the high dose group.
In the low dose group, all animals appeared ruffled up to 24 h after treatment, but appeared normal thereafter.
In the low dose group, 1/5 female died on day 6; 2/5 females exhibited diarrhea, and 1/5 exhibited diarrhea and a hunched back.

Body weight:

All animals showed body weight gain.

Gross pathology:

No gross abnormalities were noted in all animals (either found dead during the study or in the animals necropsied at the conclusion of the study).

Table 1. Results

Dose Level (mg/kg)		5000		2000
Sex		Male	Female	Male	Female
Average Body Weight (g)	Initial	243	211	219	209
	7 d	-	-	255	230
	14 d	-	-	315	258
Mortality (No. death/No. dosed)		5/5	5/5	0/5	1/5

 

Table 2: Observations:

Sex	Dose	Time after dosing	Observation
Male	2000 mg/kg	4 h 24 h 48 h to 14 d	5/5 appeared ruffled 5/5 appeared ruffled 5/5 appeared normal
	5000 mg/kg	4 h 24 h 48 h	5/5 appeared normal 3/5 found dead; 2/5 ruffled 2/5 found dead
Female	2000 mg/kg	4 h 24 h 48 h     6 d 7 d to 14 d	5/5 appeared ruffled 5/5 appeared ruffled 2/5 appeared normal, 2/5 exhibited diarrhea, 1/5 exhibited diarrhea and a hunched back 1/5 found dead; 4/5 appeared normal 4/5 appeared normal
	5000 mg/kg	4 h 24 h 48 h	5/5 appeared normal 4/5 found dead; 1/5 ruffled 1/5 found dead

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008

Conclusions:

CLP: not classified

Executive summary:

In an acute oral toxicity study, 2 groups fasted Sprague-Dawley strain Albino rats (five male and five female) were given a single oral dose of undiluted test material at a dose level of  2000 and 5000  mg/kg bw and observed for 14 days.

All animals died in the high dose group. In the low dose group, all animals appeared ruffled up to 24 h after treatment, but appeared normal thereafter. In the low dose group, 1/5 female died on day 6; 2/5 females exhibited diarrhea, and 1/5 exhibited diarrhea and a hunched back. No gross abnormalities were noted in all animals (either found dead during the study or in the animals necropsied at the conclusion of the study). All animals showed expected body weight gain during the study period.

The oral LD50 value of test material in rats of both sexes has been determined to be greater than 2000 mg/kg body weight but less than 5000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Hazard assessment is conducted by means of read-across from a structural analogue/surrogate. The selected studies are the most adequate and reliable studies based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

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

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

(occlusive)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.25-2.75 kg
- Housing: Housed individually in wire bottom cages
- Diet: approximately 4 ounces daily
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- % coverage: 100%
- Type of wrap if used: plastic sheet

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: test material removed 24 hours after exposure

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 g/kg bw

Duration of exposure:

24 h

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

yes, concurrent no treatment

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 7 and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology including: thymus, heart, lungs, liver, kidneys, adrenal glands, spleen, gonads, gastro-intestinal tract, lymph nodes, pancreas, salivary glands, bladder, body fat, skeletal muscle, teeth, eyes and skin.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

One animal with abraded skin died 13 days after dosing

Clinical signs:

Severe erythema and edema noted at 24 hours. By seven days treated sites were thick and escharotic.

Body weight:

Treated animals weighed significantly less than controls.
Average body weight during study
Control: 2.47 kg (start), 2.49 kg (day 7), 2.85 kg (day 14
Treated: 2.44 kg (start), 2.15 kg (day 7), 2.15 kg (day 14)
Note: Values are an average of 6 rabbits except for day 14 treated, which is the mean of 5 animals

Gross pathology:

Liver-like or necrotic-appearing areas of lung tissue observed in five rabbits. Further histology of the lungs revealed confluent bronchipneumonia or chronic interstitial pneumonia. Two rabbits had small white liver abscesses that were determined to be of parasitic origin after histological examination.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Hazard assessment is conducted by means of read-across from a structural analogue/surrogate. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Additional information

Justification for read-across

There are no reliable data available regarding acute toxicity forPhosphorodithioic acid, O,O-di-dodecyl-esters, zinc salts, neutral and basic(CAS 4563-56-8). Read-across from an appropriate substance Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.5. Common functional groups, structural similarities and comparable toxicological properties of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity: CAS 4259-15-8

A reliable acute toxicity study conducted with Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) in male Sprague-Dawley rats similar to OECD Guideline 401 was available (WoE, 1975). In this study the test substance was orally administered by gavage at doses of 2200, 3300, 5000 and 7500 mg/kg bw, and thereafter observed for 14 days. Mortality was observed at all dose levels, at 2200 mg/kg bw 2/10 rats died, at 3300 mg/kg bw 6/10 rats died, at 5000 mg/kg bw 9/10 rats died and at 7500 mg/kg bw all animals died. In addition, clinical signs, such as depression and diarrhea, reduced food intake and lower body fat content were noted (not further specified). Based on the results of the conducted study, a LD50 of 3100 mg/kg bw was derived for male rats.

In a second reliable acute oral toxicity study a single dose of the undiluted test material Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) was administered by gavage to ten fasted rats (5 males and 5 females) at each treatment level 2500 or 5000 mg/kg bw and observed for 14 days according to Section 1500.3 and under GLP (WoE, 1983). All animals died in the high dose group. In the low dose group, all animals appeared ruffled up to 24 h after treatment, but appeared normal thereafter. In the low dose group, 1/5 female died on day 6; 2/5 females exhibited diarrhea, and 1/5 exhibited diarrhea and a hunched back. No gross abnormalities were noted in all animals (either found dead during the study or in the animals necropsied at the conclusion of the study). All animals showed expected body weight gain during the study period. The oral LD50 value of test material in rats of both sexes has been determined to be greater than 2000 mg/kg bw but less than 5000 mg/kg bw.

Acute dermal toxicity: CAS 4259-15-8

In an acute dermal toxicity study conducted similar to OECD 402 6 male rabbits were exposed to undiluted Zinc bis[O,O-bis(2-ethylhexyl)] bis(dithiophosphate) (CAS 4259-15-8) at a dose level of 5000 mg/kg bw under occlusive conditions (Bullock, 1975). The fur of all rabbits was clipped one day prior to testing. 3/6 rabbits were further prepared by abrading the skin with a hypodermic needle. The animals were observed 14 days for signs of systemic toxicity and mortality. 1/3 rabbits with abraded skin died 13 days after dosing. Severe erythema and edema were noted at 24 hours. By seven days treated sites were thick and escharotic. Liver-like or necrotic-appearing areas of lung tissue observed in five rabbits. Further histology of the lungs revealed confluent bronchopneumonia or chronic interstitial pneumonia. Two rabbits had small white liver abscesses that were determined to be of parasitic origin after histological examination. Based on the results of the conducted study, the LD50 was derived to be > 5000 mg/kg bw.

Justification for classification or non-classification

Applying the RA-approach, the available data on acute oral and dermal toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.