Reaction mass of (Z)-1-chloro-1-propene and 2-chloropropane and 2-chloropropene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed according to OECD guideline n° 423

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-chloropropene

EC Number:

209-187-5

EC Name:

2-chloropropene

Cas Number:

557-98-2

Molecular formula:

C3H5Cl

IUPAC Name:

2-chloroprop-1-ene

Constituent 2

Reference substance name:

2-chloropropane

EC Number:

200-858-8

EC Name:

2-chloropropane

Cas Number:

75-29-6

Molecular formula:

C3H7Cl

IUPAC Name:

2-chloropropane

Constituent 3

Reference substance name:

1-chloropropene

EC Number:

209-675-8

EC Name:

1-chloropropene

Cas Number:

590-21-6

IUPAC Name:

1-chloroprop-1-ene

Details on test material:

Identification Reaction mass containing mainly 2-chloropropene
Molecular formula C3H5Cl
Molecular weight 76.53
CAS Number 557-98-2
Description Clear light yellow to brown liquid (determined at NOTOX)
Batch RBA100301A
Purity Minimum 60.0%
Test substance storage In refrigerator (2-8°C) in the dark
Stability under storage conditions Stable
Expiry date 08 March 2011 (allocated by NOTOX, 1 year after receipt of the test substance)

Specific test substance information:
General information Extremely flammable
Test substance handling If necessary, handling after sampling will be performed on dry ice in order to keep the test substance liquefied
Density 0.9
Stability in vehicle:
• Corn oil Not indicated
Solubility in vehicle:
• Corn oil Not indicated

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Test system:
Species Rat, Wistar strain Crl:WI (Han) (outbred, SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. OECD, EC).
Source: Charles River Deutschland, Sulzfeld, Germany.
Number of animals 6 Females (nulliparous and non-pregnant). Each dose group consisted of 3 animals.
Age and body weight Young adult animals (approx. 8 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex
mean.
Identification Earmark.
Health inspection A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good
state of health.

Animal husbandry:
Conditions
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0ºC (actual range: 19.7 – 21.5ºC), a relative humidity of 40-70% (actual range: 38 - 75%) and 12 hours artificial fluorescent light and 12 hours darkness per day.

Accommodation
Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

Diet
Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).

Water
Free access to tap water.

Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Method Oral gavage, using plastic feeding tubes. The formulations were kept in a bath with crushed ice during dosing. Cooled syringes and feeding tubes were used for dosing.

Fasting Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was
available.

Frequency Single dosage, on Day 1.

Doses:

2000 mg/kg (10 mL/kg) body weight.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Lethargy, hunched posture and/or piloerection were noted for all animals on Days 1 and 2. Ptosis was noted among the animals on Day 1.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The oral LD50 value of Reaction mass containing mainly 2-chloropropene in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, Reaction mass containing mainly 2-chloropropene does not have to be classified and has no obligatory labeling requirement for acute oral toxicity according to the:
- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures.

Executive summary:

The study was carried out based on the guidelines described in:

OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method"

EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

JMAFF guidelines (2000) including the most recent partial revisions.

 

Reaction mass containing mainly 2-chloropropene was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

 

No mortality occurred.

 

Lethargy, hunched posture and/or piloerection were noted for all animals on Days 1 and 2. Ptosis was noted among the animals on Day 1.

 

The body weight gain shown by the animals over the study period was considered to be normal.

 

No abnormalities were found at macroscopic post mortem examination of the animals.

 

The oral LD50 value of Reaction mass containing mainly 2-chloropropene in Wistar rats was established to exceed 2000 mg/kg body weight.

 

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

 

Based on these results, Reaction mass containing mainly 2-chloropropene does not have to be classified and has no obligatory labeling requirement for acute oral toxicity according to the:

- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007)

-   Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures.