Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.716 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
36
Modified dose descriptor starting point:
NOAEC
Value:
61.79 mg/m³
AF for intraspecies differences:
5
Justification:
worker default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.973 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
36
Modified dose descriptor starting point:
NOAEL
Value:
35.045 mg/kg bw/day
AF for intraspecies differences:
5
Justification:
worker default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Toxicokinetics:

Studies on human volunteers who were orally exposed to low concentrations of chloral hydrate indicated that Chloral hydrate is rapidly metabolized after oral absorption to produce metabolites that are excreted predominantly in urine. It also has extremely short terminal half-life of 8 to 60 min after administration at very low concentrations. Thus, it can be concluded that chloral hydrate is likely to exhibit low bio-accumulation potential.

Acute Toxicity (Oral, Dermal, Inhalation):

Based upon the study results and available information, the substance Chloral hydrate is expected to show acute toxicity effect by the oral route and thus will be considered for further classification. Though available data indicates acute oral toxicity in category 4, since the chemical chloral hydrate has a harmonized classification of Acute oral toxicity Category 3, the same has been considered for Acute oral classification.

Available data indicates that the substance is not likley to exhibit acute toxicity by the inhalation route of exposure. Also considering the use of the chemical as a sedative/hypnotic in medicine, exposure by the dermal route is highly unlikely.

Irritation effect (Skin & Eye):

The chemical chloral hydrate has a harmonized classification as "Skin irritant 2 and "Eye Irritant 2" as per the CLP criteria.

Skin sensitization:

Skin sensitizing reaction was performed in guinea pigs usingGuinea pig maximisation test. 3-4 guinea pigs were used for primary irritation studies. Later on induction and challenge exposure were performed on 7 groups with 10-14 animals.

For Induction, dorsal skin in the scapular region was shaved and after 24 hrs 3 intradermal injections were injected. Control animals were supplied with vehicle only.

After intradermal induction, animals were challenged by topical application of test agent by closed patch test and observed for 24 hrs and 48 hrs. Based on percentage of animals sensitized the grading of allergenicity was calculated.

Therefore, from the above experiment chloral hydrate (302-17-0) was found to be not sensitizing to guinea pig.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.423 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEC
Value:
30.474 mg/m³
AF for intraspecies differences:
10
Justification:
general population default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.487 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Value:
35.045 mg/kg bw/day
AF for intraspecies differences:
10
Justification:
General population default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.243 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Value:
17.523 mg/kg bw/day
AF for intraspecies differences:
10
Justification:
general population default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

DNEL derivation

2,2,2-trichloroethane-1,1-diol exhibits acute toxicity by oral route of exposure and thus will be considered in acute toxic category 3 for classification (Harmonized Classification).

Chloral hydrate was found to have Harmonized Classification of Skin Irritation 2 and Eye Irritation 2. Available data also indicates that the chemical does not exhibit genotoxicity and is not a reproductive toxin within the dose levels mentioned in the end points  

In the absence of local effects following short-term or long-term exposure, no dose-response data are available and a quantitative dose descriptor is not derived. DNEL values for local exposure are therefore not calculated.   In the absence of acute systemic toxicity, no dose-response data are available and a quantitative dose descriptor is not derived. DNEL values for acute systemic effects are therefore not calculated.  

A standard approach to deriving DNEL values would be to use the developmental dose toxicity dataset and apply assessment factors as described in ECHA guidance documents. The critical endpoint is considered to be the NOAEL of 70.09 mg/kg bw/d in oral category.