Dodecanoic acid, ester with oxybis[propanediol]

Endpoint summary

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 20,000 mg/kg bw (FDA, 1959)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: National guideline study with acceptable restrictions.

Qualifier:

according to guideline

Guideline:

other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics" by the Staff of the Division of Pharmacology, FDA, 1959

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Zucht Winkelmann, Paderborn, Germany
- Weight at study initiation: 120-145 g (males), 115-145 g (females)
- Fasting period before study: 16 h
- Housing: single caging
- Diet: standard laboratory diet (Ssniff/Intermast), ad libitum.
- Water: ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50%
- Amount of vehicle: 20 and 40 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 40 mL/kg bw

DOSAGE PREPARATION: The test substance was diluted to a final concentration of 50% in olive oil.

- Rationale for the selection of the starting dose: Based on a range-finding study (not further information), doses of 10 and 20 g/kg bw were selected for the determination of the LD50 value.

Doses:

10,000 and 20,000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: animals were observed for clinical signs 20 min and 1, 3, 24 and 48 h and 7 days after administration. Individual body weights were determined at Day 0 (study initiation) and at the end of the observation period (Day 7).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and gross necropsy

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Based on:

test mat.

Mortality:

10,000 mg/kg bw: 0/5 males and 0/5 females died.
20,000 mg/kg bw: 1/5 males and 1/5 females were found dead at 48 h post treatment.

Clinical signs:

other: At 10,000 and 20,000 mg/kg bw, piloerection, slight staggering and ataxia were observed 1 and 3 h after administration (no further information on number of animals). The effects were reversible within 24 h.

Gross pathology:

No changes were observed at gross necropsy of dead and sacrificed animals of the examined organs (brain, lung, heart, stomach, intestines, liver, spleen, kidneys, serous membrane/vessels, lymph nodes and gonads).

Table 1.Results of acute oral toxicity experiment. 

Does [mg/kg bw]	Mortalities [No. of animals/No. in group]	Time of death (post-treatment)	Mortality [%]	Clinical signs / Duration
Males
10,000	0/5	-	0	Staggering, ataxia, piloerection / 1-3 h post-dose
20,000	1/5	48 h	20	Staggering, ataxia, piloerection / 1-3 h post-dose
Females
10,000	0/5	-	0	Staggering, ataxia, piloerection / 1-3 h post-dose
20,000	1/5	48 h	20	Staggering, ataxia, piloerection / 1-3 h post-dose

Table 2. Body weight and body weight gain. 

Animal number	Body weight on Day 0 [g]	Body weight on Day 7 [g]	Body weight gain [%]
Males (10,000 mg/kg bw)
1	130	155	19
2	135	160	19
3	120	135	13
4	140	150	7
5	145	165	14
Mean	134	153	14
Females (10,000 mg/kg bw)
1	120	145	21
2	115	130	13
3	130	155	19
4	120	145	21
5	140	160	14
Mean	125	147	18
Males (20,000 mg/kg bw)
1	140	- (dead)	-
2	145	155	7
3	135	120	-11
4	140	145	4
5	145	155	7
Mean*	141.25	143.75	2
Females (20,000 mg/kg bw)
1	135	160	19
2	135	150	11
3	145	105	-28
4	140	- (dead)	-
5	145	160	10
Mean*	140	143.74	3

 *Calculations based on surviving animals

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral

There are no data available on the acute oral toxicity of Reaction product of lauric acid and oxybis(propanediol) (List No. 700-672-1). In order to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related surrogate substance 2,3-dihydroxyproypl laurate (CAS No. 142-18-7) was conducted.

Reaction product of lauric acid and oxybis(propanediol) mainly consists of diglycerol monoesters with lauric acid (C12). Therefore, available data on the acute oral toxicity of the structural surrogate, 2,3-dihydroxyproypl laurate (CAS No. 142-18-7), a glycerol monoester with lauric acid (C12), was considered for read-across and assessment was conducted based on an analogue approach.

The acute toxicity of 2,3-dihydroxyproypl laurate after oral administration was investigated in a test conducted according to the “Appraisal of the safety of chemicals in foods, drugs and cosmetics, FDA, 1959” (Sterner, 1977). Groups of 5 male and 5 female Wistar rats per dose were given 10,000 or 20,000 mg/kg bw of the test substance by gavage and the animals were observed for a period of 7 days following administration.

During the study period, 1/5 males and 1/5 females died in the high-dose group 48 h after administration. Clinical signs including slight staggering, ataxia and piloerection were observed 1 and 3 h post-dose in several animals (not further specified) being reversible within 24 h. At 20,000 mg/kg bw, the average body weight gain was reduced in both females and males due to strongly decreased body weight of 1 animal in each group. Gross necropsy of dead and sacrificed animals did not reveal any changes of the examined organs.

Therefore, the oral LD50 for male and female rats was considered to be greater than 20,000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. 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).

Justification for classification or non-classification

Based on read-across from a surrogate substance following an analogue approach, the available data on acute toxicity of Reaction product of lauric acid and oxybis(propanediol) (List No. 700-672-1) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.