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Administrative data

Description of key information

Oral:
-LD50 > 2000 mg/kg bw (based on test material) / LD50 > 830 mg a.i./kg bw; OECD TG 423, rat (female) oral: gavage (RL1, GLP); read-across: Formamidopropylbetaine
-LD50 = 2335 mg a.i./kg bw; Similar to OECD TG 401, standard acute method, rat oral: gavage (RL1; pre-GLP); read-across: C8-18 and C18 unsatd. AAPB
Dermal:
-LD50 > 2000 mg a.i./kg bw; OECD TG 402, rat, Type of coverage: Occlusive (RL1, GLP); read-across: Formamidopropylbetaine
-LD50 > 2000 mg/kg bw (based on test material) / LD50 > 620 mg a.i./kg bw; OECD TG 402, rat, Type of coverage: Occlusive (RL1, GLP); read-across: C8-18 and C18 unsatd. AAPB
Inhalation
-No relevant route of exposure

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

No experimental data are available for the target substance Undecylenamidopropyl Betaine. However, acute oral and dermal toxicity studies are available for the closely related source substances C8-18 and C18 unsatd. AAPB (Coco AAPB) and Formamidopropylbetaine. A justification for read-across is given below.

 

Acute oral toxicity

In an acute oral toxicity study according to US Guideline Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics, FDA, 1959, which is comparable to the OECD guideline 401 (1981), 5 male and 5 female Wistar rats were given a single oral dose of Coco AAPB (30 % a.i.) as delivered by the sponsor at doses of 5.0, 6.3, 7.94, and 10.0 mL/kg bw. Animals were then observed for 14 days.

At 5.0, 6.3, 7.94, and 10.0 ml/kg bw 2/10, 2/10, 6/10, and 8/10 animals died, respectively. Most animals died within 24 hours p.a.. Weight gains were normal in all animals. Clinical signs at >= 5 mL/kg bw were decreased motor activity, coordination disturbances, abnormal body posture, piloerection, diarrhoea, skin/mucosa cyanosis and decreased body temperature with dose response relationship. At >= 7.94 mL/kg bw animals showed prone position. Clinical signs were observed at 20 minutes, 1 h and 3 h after application. Except of slight diarrhoea in one animal in dose groups 6.3, 7.94 and 10 mL/kg bw, each, all symptoms were reversible after 24 hours. 7 days after application, all surviving animals were free of clinical symptoms. Gross pathology examination of animals found dead revealed reddened gastric and intestinal mucosa. Animals sacrificed at study termination 14 days p.a. had light reddened intestinal mucosa.

Oral LD50 Combined = 7.45 mL/kg bw after 14 d

Oral LD50 Combined = 8.1 mL/kg bw after 24 h

LD50 determined refers to the test substance as delivered by the sponsor. There is no information on content of active ingredient of the test substance in the study report. However, according to producer information tested Coco AAPB has 30% active ingredient. The density is roughly 1 g/mL. Therefore, the calculated oral LD50 combined referring to 100% active substance = 2335 mg/kg bw after 14 d.

Coco AAPB is of low toxicity based on the LD50 in males and females.

 

In an acute oral toxicity study according to according to the OECD Guideline for the Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method” 6 female Wistar rats were given a single dose of Formamidopropylbetaine (50% based on solid matter, active matter: 41.5%).

The test substance was applied by gavage undiluted and as 10% (w/w) solution in tap water. No toxic symptoms after administration of 300 mg/kg body weight were observed in six animals. In the next step the test substance was applied to six rats at a dose level of 2000 mg/kg body weight. No toxic symptoms were observed in this group, as well. No death occurred in all groups of the dose levels 300 mg/kg and 2000 mg/kg body weight. Body weight development of all animals was positive 7 days and 14 days post application. The necropsy 14 days after oral application showed no substance related morphological visible pathologic organ findings. Thus, the LD50-value for the test substance is higher than 2000 mg/kg bw, corresponding to > 830 mg/kg bw in terms of active substance.

 

Based on these results, the oral LD50 of the target substance Undecylenamidopropyl Betaine is considered to be >2000 mg/kg bw.

 

Acute dermal toxicity

In an acute dermal toxicity study according to EU Method B.3 and OECD Guideline 402, 5 male and 5 female CD rats (Crl:COBS CD(SD)BR) were dermally exposed to Coco AAPB (a.i 31 %) as delivered by the sponsor for 24 hours to 10% of total body surface at a dose of 2000 mg/kg bw (limit test). Test sites were covered with an occlusive dressing. After 24 hours, the test sites were rinsed with warm water. Animals then were observed for 14 days after dosing.

There were no clinical signs of systemic reaction to treatment. Sites of application of the test substance showed slight or well-defined erythema in all animals on Day 2 and/or 3. On Day 4 and Day 5, slight erythema were seen in three male and four female rats, sloughing in two male rats and one female rat and hyperkeratinisation in three female rats. All skin reactions were completely reversible by Day 6 in all animals. Slightly low bodyweight gains were recorded for three females on Day 8. All other rats achieved anticipated bodyweight gains throughout the study. Terminal autopsy findings were normal.

Dermal LD0 Combined: 2000 mg/kg bw

Dermal LD50 Combined: > 2000 mg/kg bw

LD0 and LD50 determined refer to the test substance as delivered by the sponsor. Amount of active ingredient in test substance is 31 %. Therefore the calculated oral LD0and LD50 combined referring to 100 % active substance is 620 and > 620 mg/kg bw, respectively.

Coco AAPB (a.i. 31 %) is of low toxicity based on the LD50 in males and females.

 

In an acute dermal toxicity study according to OECD Guideline 402 (1987) "Acute Dermal Toxicity" and EC, Council Directive 67/548/EEC, Annex V, B.3 (1992) Formamidopropylbetaine was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred, Chromodacryorrhoea was noted among the animals on days 1 and 2, Scales were seen in the treated skin-area of some animals between days 3 and 12. The body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of Formamidopropylbetaine in Wistar rats was established to exceed 2000 mg/kg body weight (corrected for purity of the test substance).

 

Based on these results, the dermal LD50 of the target substance Undecylenamidopropyl Betaine is considered to be >2000 mg/kg bw.

 

Acute inhalation toxicity

Acute toxicity studies by inhalation route are unjustified. Due to its very low vapour pressure, an exposure to Undecylenamidopropyl Betaine vapour is negligible. Generation of aerosols may be theoretically possible, however the estimated exposure is very low. Furthermore, systemic toxicity relevant to humans did not appear neither in acute nor in repeated dose toxicity studies by other exposure routes. Considering the exposure probability and the available information on the intrinsic toxic activity of the substance, an inhalative risk to humans is unlikely and therefore, conduct of an inhalative toxicity study is unjustified.

 

Summary

There is no evidence on relevant intrinsic acute toxic activity of Undecylenamidopropyl Betaine constituting a hazard to human health. The acute toxicity of closely related source substance in rats was demonstrated to be low, with a dermal LD50 > 2000 mg/kg bw, and an oral LD50 value of 2335 mg/kg bw.

 

There are no data gaps for the endpoint acute toxicity. No human data are available. However, there is no reason to believe that these results from rat would not be applicable to humans.

 

 

Justification for read-across

For details on substance identity and detailed toxicological profiles, please refer also to the general justification for read-across given at the beginning of the CSR and attached as pdf document to IUCLID section 13.

 

This read-across approach is justified based on structural similarities. The target and source substances contain the same functional groups. Thus a common mode of action can be assumed.

The only deviation within this group of substances is a variety in their carbon chain length, which obviously does not have a relevant impact on acute toxicity as demonstrated by the available data on the source substances.

 

 

Structural similarity and functional groups

The target substance Undecylenamidopropyl Betaine is a monoconstituent substance manufactured from undecylenic acid and N, N-dimethylpropylenediamine (DMAPA) and further reacted with monochloroacetic acid.

The source substance C8-18 and C18 unsatd. AAPB is a UVCB substance manufactured from natural fatty acids or oils with N, N-dimethylpropylenediamine (DMAPA) and further reacted with sodium monochloroacetate. As their origin is from natural sources, the used fatty acids may have a mixed slightly varying composition with an even numbered chain length from C8 to C18, including unsaturated C18 chains.

 

The source substance Formamidopropylbetaine is a monoconstituent substance manufactured from formic acid and N, N-dimethylpropylenediamine (DMAPA) and further reacted with sodium monochloroacetate.

 

Differences

Differences in chemical and other intrinsic properties of the target and source substances could potentially arise from the following facts:

-Different amounts of different carbon chain lengths (carbon chain length distribution):

Higher amounts of higher chain lengths and corresponding lower amounts of lower chain length lead to a rising average lipophilicity as can be seen from the increasing log Kow from Formamidopropylbetaine (log Kow: -3.3), Undecylenamidopropyl Betaine (log Kow: -1.38), C12 AAPB (log Kow: 3.54), C8-18 and C18 unsatd. AAPB (log Kow: 4.23).

Interpolation from Formamidopropylbetaine and C8-18 and C18 unsatd. AAPB is considered to be appropriate to fulfil the information requirements for acute oral and dermal toxicity.

 

- Different amounts of unsaturated fatty ester moieties:

The source substance C8-18 and C18 unsatd. AAPB contains considerable amounts of unsaturated C18 chains, which represents a worst case with respect tosome toxicological endpoints, mainly local effects (e.g. irritation, sensitisation).

 

The provided structural similarities and impurity profiles support the proposed read-across hypothesis with high confidence.

 

Comparison of acute toxicity data

Endpoints

Source substance

Target substance

Source substance

 

Formamidopropylbetaine

Undecylenamidopropyl Betaine 

C8-18 and C18 unsatd. AAPB

Acute toxicity, oral

 

WoE_RA_LTOE 16396 Acute toxicity: oral

 

OECD TG 423, rat (female) oral: gavage

 

LD50 > 2000 mg/kg bw (based on test material)

LD50 > 830 mg a.i./kg bw

 

Reliability: 1 (reliable without restrictions), GLP

No data, read-across

WoE_RA_Acute toxicity: oral: 61789-40-0_8.5.1_Th_Goldschmidt_AG_1977

 

Similar to OECD TG 401, standard acute method, rat oral: gavage


LD50 = 7.45 mL/kg bw (based on test material; after 14 d)

LD50 = 2335 mg a.i./kg bw (after 14 d)
LD50 = 8.1 mL/kg bw (based on test material; after 24 h)
LD50 = 2430 mg a.i./kg bw (after 24 h)

Reliability: 1 (reliable without restrictions), pre-GLP

Acute toxicity, dermal

WoE_RA_NOTOX 454027 Acute toxicity: dermal

 

OECD TG 402, rat, Type of coverage:

Occlusive

 

LD50 > 2000 mg a.i./kg bw

 

Reliability: 1 (reliable without restrictions), GLP

No data, read-across

WoE_RA_Acute toxicity: dermal: 61789-40-0_8.5.3_KAO Corporation_1987_OECD 402

 

OECD TG 402, rat, Type of coverage:

Occlusive


LD0 > 2000 mg/kg bw (based on test material)
LD0 > 620 mg a.i./kg bw
LD50 > 2000 mg/kg bw (based on test material)

LD50 > 620 mg a.i./kg bw

 

Reliability: 1 (reliable without restrictions), GLP

 

There is no evidence of relevant intrinsic acute toxicity of the source substances:

-      The oral LD50 of C8-18 and C18 unsatd. AAPB was 2335 mg a.i/kg bw in rat.

-      The oral LD50 of Formamidopropylbetaine was > 2000 mg/kg bw (based on test material), corresponding to LD50 > 830 mg a.i./kg bw

-      Although C8-18 and C18 unsatd. AAPB has only been tested at 620 mg a.i./kg bw (corresponding to 2000 mg/kg bw in terms of test material) via the dermal route, the consideration of all available data on acute dermal toxicity, acute oral toxicity, toxicokinetics and dermal penetration leads to the conclusion, that the dermal LD50 will be > 2000 mg a.i./kg bw.

-      This is supported by the dermal LD50 of Formamidopropylbetaine of > 2000 mg a.i./kg bw

 

The source substances Formamidopropylbetaine and C8-18 and C18 unsatd. AAPB represent both extremes with shorter and longer C-chains compared to the target substance Undecylenamidopropyl Betaine. C8-18 and C18 unsatd. AAPB also contains higher amounts of unsaturated fatty acid chains. Interpolation is judged to be appropriate to fulfil the information requirements for this endpoint.

 

Quality of the experimental data of the analogues:

The available data are adequate and sufficiently reliable to justify the read-across approach.

The acute oral toxicity of C8-18 and C18 unsatd. AAPB was tested in a study similar to OECD Guideline 401 (RL1, study performed before implementation of GLP). The acute oral toxicity of Formamidopropylbetaine was tested in a study according to OECD Guideline 423 (RL1, GLP).

The acute dermal toxicity of C8-18 and C18 unsatd. AAPB as well as Formamidopropylbetaine was tested in a study according to OECD Guideline 402 (RL1, GLP).

The test materials used in the respective studies represent the source substance as described in the hypothesis in terms of substance identity and minor constituents.

Overall, the study results are adequate for the purpose of classification and labelling and risk assessment.

 

Conclusion

Based on structural similarities of the target and source substances as presented above and in more detail in the general justification for read across, it can be concluded that the available data from the source substances C8-18 and C18 unsatd. AAPB and Formamidopropylbetaine are also valid for the target substance Undecylenamidopropyl Betaine.

There is no evidence of relevant intrinsic acute toxicity of Undecylenamidopropyl Betaine, thus, classification and labelling with regard to acute toxicity is not warranted.


Justification for selection of acute toxicity – oral endpoint
No single key study has been selected, since all available data are used on a weight of evidence approach.

Justification for selection of acute toxicity – dermal endpoint
No single key study has been selected, since all available data are used on a weight of evidence approach.

Justification for classification or non-classification

Based on the available data, Undecylenamidopropyl Betaine does not need to be classified for acute toxicity according to regulation (EC) 1272/2008. Thus, no labelling is required.