4-[(morpholinothio)thioxomethyl]morpholine

Endpoint summary

Description of key information

Acute Oral Toxicity:  Two Acute Oral LD50 studies were conducted in rats. The lowest LD50 in these studies was 5000 mg/kg. An acute oral LD50 study was conducted in mice.  The LD50 in this study was 9000 mg/kg.

Acute Dermal Toxicity: The acute dermal LD50 for albino rabbits is greater than 10,000 mg/Kg.

Acute Inhalation Toxicity: The acute inhalation LC50 (1hr) is greater than 164.4 mg/L.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

discriminating dose

Value:

10 000 mg/kg bw

Additional information

Acute Oral Toxicity:

An acute oral toxicity test was performed to determine the acute toxicity by oral exposure of Cure-rite 18 in rats (Biodynamics 1980, 6216 -80).

Five groups of ten rats (5 males and 5 females) were dosed at the following concentration: 1800, 2700, 4050, 6075 and 9112 mg test substance/kg bodyweight by oral gavage; observation for mortality and clinical signs was performed over a period of 14 days. At the end of the observation period, all animals were sacrificed and postmortem examinations performed.

0/10 rats died in the 1800 mg/kg dose group 1/10 rats died in the 2700 mg/kg dose group, 1/10 rats died in the 4050 mg/kg dose group, 9/10 rats died in the 6075 mg/kg dose group, 8/10 rats died in the 9112 mg/kg dose group. A considerable number of physical observations noted during the 14 day observation period. The most common findings were decreased respiratory rate and clear ocular, oral or nasal discharge.

The acute lethal oral dose to rats of Cure-rite 18 was found to be 5,000 mg/kg bodyweight for rats from 1 supplier and 5,200 mg/kg bodyweight for rats from a second supplier.

In a second study performed to determine the acute toxicity by oral exposure of Cure-rite 18 in mice (Biodynamics 1980, 6217 -80).

Five groups of ten mice (5 males and 5 females, except 1 group with 6 males and 4 females) were dosed at the following concentration: 1800, 2700, 4050, 6075 and 9112 mg test substance/kg bodyweight by oral gavage; observation for mortality and clinical signs was performed over a period of 14 days. At the end of the observation period, all animals were sacrificed and postmortem examinations performed.

One male and one female dosed at 1800 and 4050 mg/kg respectively died due to dosing accidents. 1 died at 6075 mg/kg and 6 died at 9112 mg/kg. Fecal staining and soft stool were common findings in both sexes. Motor activity decrease and poor food consumption were the only other consistent findings.

The acute lethal oral dose to mice of Cure-rite 18 was found to be 9,000 mg/kg bodyweight.

A third acute oral toxicity test was performed to determine the acute toxicity by oral exposure of Cure-rite 18 on rats (Hilltop, 1979, V 918).

Five groups of 5 male rats were dosed at the following concentration: 464, 1,000, 2,150, 4,640 and 10,000 mg test substance/kg bodyweight by oral gavage; observation for mortality and clinical signs was performed over a period of 14 days. At the end of the observation period, all animals were sacrificed and postmortem examinations performed.

0/5 rats died in the 464 and 1,000 mg/kg dose groups 1/5 rats died in the 2150 mg/kg dose group, 1/5 rats died in the 4640 mg/kg dose group, 5/5 rats died in the 10,000 mg/kg dose group. Depression, depressed reflexes, lacrimation, diarrhea and emaciation were recorded at the highest dose level. Similar signs were seen at all dose levels, but subsided steadily at lower dose levels..

The acute lethal oral dose to rats of Cure-rite 18 was found to be 5,110 mg/kg bodyweight.

Acute inhalation toxicity

An acute toxicity study was conducted to assess the toxicity of Cure-rite 18 after acute inhalation exposure (Hilltop 1971, V-918)

Ten male rats were exposed by whole body exposure to an atmosphere containing the test material as an airborne dust for an exposure period of one hour. Following the exposure process, animals were observed for 14 days, sacrificed, then a necroscopic examination performed.

There were no deaths during the study. Test substance residues were seen on the fur of most of the exposed rats. Serosanguineous lacrimation and nasal discharge was noted in occasional rats in first few days of the study. Followed by normal appearance for the remainder of the 14 day observation period. Gross necropsy revelaed no pathological alterations.

The1-hour LC50 was estimated to be in excess of 164.4 mg/L of air in rat.

 

Acute dermal toxicity

The toxicity of Cure-rite 18 was assessed after acute dermal exposure (Hilltop 1971, V-918).

Four groups consisting of four rabbits each were exposed to the test substance by dermal exposure at 1.0, 2.15, 4.64 and 10 g/kg bodyweight for a period of 24 hours. At the end of the exposure period, the test substance was washed off, and the test animals were observed for mortality, clinical signs and signs of dermal irritation for a period of 14 days after exposure. At the end of the observation period, all test animals were sacrificed and post mortem examinations were performed.

One rabbit (Rabbit 4) in the 1.0 mg/kg group was found dead on day 8. No other deaths occurred in the test animals during the exposure or observation periods. Observation of Rabbit 4 showed slight emaciation, nasal discharge and wheezing noted on the 6th and 7th post-exposure day. Death followed on day 8. For the remaining animals, a few exhibited slight ataxia at completion of the exposure period only. Emaciation in four rabbits and a purulent nasal discharge in several animals were noted. The surviving rabbits exhibited normal appearance and behavious throughout the study.

The acute lethal dermal dose to rabbits of Cure-rite 18 was found to be greater than 10.0 g/kg bodyweight. 

Justification for classification or non-classification

The acute toxicity results for Cure-rite 18 were reviewed with reference to EC directive 67/548/EEC, and the EU interpretation of CLP, EU Regulation 1272/2008. On the basis that the available tests confirmed the oral LD₅₀value to be greater than 5000 mg/kg bodyweight, the dermal LD₅₀value to be greater than 2000 mg/kg bodyweight, and the inhalation LC50 value to be greater than 5 mg/l. Cure-rite 18 does not require classification as toxic by oral, dermal or inhalation exposure.