Registration Dossier

Administrative data

Description of key information

- Oral:           LD50: 120 mg/kg bw for the male rat (OECD TG 401); study Shell Development Company (1980a))
- Dermal: LD50: 390 mg/Kg bw for the male rabbit (OECD TG 402); study Shell Development Company (1980b)
- Inhalation: LC50(4 h): >= 4800 mg/kg bw for the rat (OECD TG 403); study Monsanto Company (1987)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
120 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
4 800 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
390 mg/kg bw

Additional information

- oral toxicity:

A LD50(oral, Sprague-Dawley rat, male) of 120 mg/kg bw is reported in the key study Shell Development Company (1980a) / key (rat acute oral toxicity, reliability Klimisch 2). The LD50(oral, rat, female) is 180 mg/Kg bw and the LD50 (oral, rat, combined) for both sexes is 152 mg/Kg bw. In the second available study that is also reliable (Monsanto Company (1985) / (rat, acute oral toxicity); Klimisch 2) comparable LD50 values are reported (Sprague-Dawley rats, males: 205 mg/Kg bw; females 170 mg/Kg bw). So both studies suggest a slight difference in the susceptibility of the two sexes to acute toxicity of 1,2,3-trichloropropane. Both studies report comparable clinical signs: (ataxia; decreased activity/prostration; hypopnea; wet rales; nasal/oral/ocular discharge; soft stool; fecal and urinary staining; decreased food consumption and unthrifty coat) and comparable necropsy findings(changes in the stomach/intestines suggested of irritation or corrosive effect (red or black foci in stomach walls, presence of red or black material and discoloration of walls); some red or brown fluid in the urinary bladder; and red foci and discoloration of the lungs and other organs of the central cavities and testes drawn into abdominal cavity ).

No additional data for other species is available. As the rat is the standard model organism for acute toxicity testing, these results are deemed sufficient for classification & labelling purposes and hazard assessment.

- dermal toxicity:

A LD50(NewWhite, rabbit, male) LD50 (dermal, rabbit, male) = 390 mg/Kg bw is reported in the key study of Shell Development Company (1980b) / key (rabbit acute dermal toxicity, reliability Klimisch 2). The LD50 (dermal, rabbit, female) is 765 mg/Kg bw and the combined LD50 (dermal, rabbit, combined) for both sexes is 523 mg/Kg bw In the second available study that is also reliable Monsanto Company (1985) / (rabbit, acute dermal toxicity; Klimisch 2) slightly higher values are reported (New Zealand White rabbits, LD50 (dermal, rabbit, male) = 900 mg/Kg bw , LD50 (dermal, rabbit, female) = 850 mg/Kg bw LD50 (dermal, rabbit, combined) = 880 mg/Kg bw). So in the Shell study a notably sex difference was seen as in rats in acute oral toxicity, while in the Monsanto study no such difference was obvious. Both studies report comparable clinical signs that are also comparable to the clinical signs in rats in the acute oral studies (activity decrease, ataxia and nasal discharge, few feces, no urination, hematuria, swollen testes/urethra, iritis, cyanosis and death). At gross necropsy comparable effects were found in both dermal studies that are in-line with findings in the acute studies in rats (discolored internal organs (kidney, lungs, urinary bladder, liver, intestines); organs distended with blood; mottled organs (kidney, liver); swollen testes; fluid in abdominal cavity and pronounced serosal blood vessels on intestines).

- inhalation toxicity:

Diverging data is available for inhalation toxicity. In a study that was deemed reliable in SIDS dossier on 1,2,3-trichloropropane (Monsanto Company (1987) / (rat, acute respiratory toxicity)) toxicity was apparent but did not lead to mortality at the used limit dose of 4800 mg/m³. The reported clinical signs were hypoactivity, lacrimation and slow labored breathing during exposure and periocular wetness, clear nasal discharge, hypoactivity, labored respiration, gasping, rattling sounds in lungs, red/brown perinasal encrustation and ataxia after exposure.

The other available studies give different results, but are all deemed unreliable for several reasons. At least they all lack information on substance purity.

Study name

LC50(4h) in mg/m³

Monsanto Company (1987) / (rat, acute respiratory toxicity)

≥ 4800

DOW K-002524-005 / (F344 rat and B6C3F1 mouse, acute inhalation toxicity)

No numerical data presented

Mice: < 740

Rats: 740 < LC50(4h) < 2000

Hazelton 776-137 / (F344 rat, 1h inhalation exposure)

Females, 1 h exposure: 8560

Females, calculated 4 h exposure: 2140

Males, 1 h exposure: 13980

Males, calculated 4 h: 3495

NIOSH RTECSfor 1,2,3-trichloropropane

Union Carbide datasheet, rat, 2h exposure 3400

Union Carbide datasheet, rat, 4 h calculated:

1700

Citation Bandman A.L. et al. 1990: lowest lethal concentration = 3050

 In addition to the lack on substance purity data, DOW K-002524-005 does not present any precise numerical data on mortalities. It is only verbally described, that all mice died at 740 mg/m³ and fatalities occurred in rats at 740 and 2000 mg/m³ while all animals survived at higher doses. Of Hazelton 776-137 pages on animal source and husbandry was missing and during the 4 h trials no mortality occurred at any of the used doses, rendering the correct functioning of the test system questionable also for the measurements at 1 h of exposure. NIOSH RTECS for 1,2,3-trichloropropane cites two sources: a Union Carbide datasheet and Bandman A.L. et al. 1990 both of which are not available. Therefore the reliability of the stated results remains unclear. Monsanto Company (1987) remains the only reliable study that nevertheless does not deliver a clear LC50 value but only an estimation for a lower limit of this threshold value.

Justification for classification or non-classification

- oral toxicity: 1,2,3-trichloropropane is moderately toxic via the oral route based on systemic effects that lead to corrosive effects in the stomach and distended organs and possibly cyanosis as final cause for death. Classification as Category III (H301: toxic if swallowed) is considered to be required according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

- dermal toxicity: 1,2,3-trichloropropane is moderately toxic via the dermal route based on systemic effects that lead to discolorated and distended organs and possibly cyanosis as final cause for death. Classification as Category III (H311: Toxic in contact with skin) is considered to be required according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

- inhalation toxicity: The results for inhalation toxicity of 1,2,3-trichloropropane are ambiguous. Based on the results of the only study deemed reliable in the SIDS report on 1,2,3-trichloropropane and following a conservative approach the substance is deem moderately toxic, Classification as Category III (Danger: H331: Toxic if inhaled) according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.