D-Gluconic acid, δ-lactone, reaction products with propanolamine

Endpoint summary

Description of key information

Key information is based on weight of evidence data from acute toxicity studies performed with the two main components aminopropanol and gluconate and dated before 2009.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

3-aminopropan-1-ol is one of the constituents of Reaction mass of 3-hydroxypropan-1-aminium D-gluconate and N-(3-hydroxypropyl)-D-gluconamide.at a molar ratio of 1:1. The process used is a pseudo acid – base reaction in water that leads always to a mixture of the “amide” and the “salt” part. Both entities are required for the applications performances. With the manufacturing process used here it is not possible to separate the amide and salt part from the water phase. The 3-aminopropan-1-ol is the kation of the salt part.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA
- Weight at study initiation: male: 220-260 g, female: 160-180 g
- Fasting period before study: 15-20 h

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 4.64, 6.85, 10, 14.7, 21,5 %

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

464, 681, 1000, 1470, 2150 mg/kg

No. of animals per sex per dose:

5 male and 5 female animals per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: before study, after 2-4 days, 7 days and 13 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 348 mg/kg bw

Mortality:

1 of 10 animals died at 464 mg/kg
1 of 10 animals died at 681 mg/kg
no animals died at 1000 mg/kg
5 of 10 animals died at 1470 mg/kg
all animals died at 2150 mg/kg

Clinical signs:

clinical signs included: apathy, dyspnoea, stertorous respiration, gasping, apathy, staggering, urine of strong yellow colour, scrubby fur, anaemic paleness, blood in nose and saliva, bad general condition. Most of these clinical signs were only observed in the two highest dose groups.

Gross pathology:

The sacrificed animals were without findings.
The following findings were made in animals that died during the study:
heart: acute right dilation
liver: circumferential delineation of the liver lobes
stomach: atonic, reddened mucosa
intestine: reddened mucosa
lung: slight emphysema

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

As one mol of Reaction mass of 3-hydroxypropan-1-aminium D-gluconate and N-(3-hydroxypropyl)-D-gluconamide contains 0.5 mol of 3-aminopropan-1-ol, and gluconic acid is not classified, its oral LC50 is > 2000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1978

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Justification for type of information:

D-gluconate is one of the main constituents of Reaction mass of 3-hydroxypropan-1-aminium D-gluconate and N-(3-hydroxypropyl)-D-gluconamide at a molar ratio of 1:1. The process used is a pseudo acid – base reaction in water that leads always to a mixture of the “amide” and the “salt” part. Both entities are required for the applications performances. With the manufacturing process used here it is not possible to separate the amide and salt part from the water phase. D-gluconate is the anion of the salt part.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

10 rats per group were exposed to 5 different dosages administered by gavage.

Deviations:

not applicable

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Not specified

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: TNO
- Age at study initiation: young adults
- Weight at study initiation: males: 240-382 g and females 156 to 206 g
- Fasting period before study: overnight
- Housing: screen-bottomed, stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 - 25
- Humidity (%): not specified
- Air changes (per hr): well-ventillated
- Photoperiod (hrs dark / hrs light): not specified

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30% w/v
- Amount of vehicle (if gavage): 10.0 to 20.7 ml per kg bw
- Justification for choice of vehicle: substance is water soluble

Doses:

3, 3.6, 4.32, 5.19, 6.21 g/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Statistics:

LD50 was calculated according to the method of Weil (Weil C S. Tables for convenient calculation of median-effective dose (LD50 or ED50) and instructions in their use. Biometrics 8:249-63, 1952).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

6 060 mg/kg bw

95% CL:

>= 5 640 - <= 6 510

Mortality:

Dosages < 5190 mg/kg: no mortality, 20% at 5190 mg/kg and 80% at 6210 mg/kg

Clinical signs:

Sluggishness, humpback behaviour and severe diarrhoea few hours after dosing, gradual recovery during observation period.

Body weight:

not specified

Gross pathology:

No findings

Other findings:

not specified

Interpretation of results:

GHS criteria not met

Conclusions:

Substance can be classified as practically non-toxic.

Executive summary:

Rats were fed by gavage 3000, 3600, 4320, 5190, 6210 mg/kg bw (30% (w/v) aqueous solution) potassium gluconate and were observed for signs of toxicity during a 14-day period. One animal

died in the 5190 mg/kg bw group and four animals in the 6210 mg/kg bw group. Deaths occurred between 5 and 21 hours after treatment. Survivors recovered gradually. The LD50 was calculated

(according to the method of Weil) to be 6060 mg/kg bw. However, the effects that were observed occurred at doses that exceed the accepted limit dose of 5000 mg/kg bw and the LD50 may be

related to high dosing.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Conclusion is based on separate studies, each with one of the constituents.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

3-aminopropan-1-ol is one of the constituents of Reaction mass of 3-hydroxypropan-1-aminium D-gluconate and N-(3-hydroxypropyl)-D-gluconamide.at a molar ratio of 1:1. The process used is a pseudo acid – base reaction in water that leads always to a mixture of the “amide” and the “salt” part. Both entities are required for the applications performances. With the manufacturing process used here it is not possible to separate the amide and salt part from the water phase. The 3-aminopropan-1-ol is the kation of the salt part.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Inhalation hazard test, animals exposed for 1 hour

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: MUS RATTUS, Brunnthal
- Weight at study initiation: 185 +/- 15 g
- Diet: Herilan MRH, ad libitum
- Water: Tap water, ad libitum

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: head-nose inhalation system
- Method of holding animals in test chamber: animals are held in a tube, the head/nose being exposed to the inhalation chamber

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gas chromatography

Duration of exposure:

1 h

Concentrations:

0, 6.64, and 16.35 mg/l analytical concentration

No. of animals per sex per dose:

10 male and 10 female animals per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: day 0, 7 and 14
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Data were anlysed according to the "Bionominaltest" (Wittig H, Mathematische Statisik, 1974, pp 32-35)

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 16.4 mg/L air (analytical)

Exp. duration:

1 h

Mortality:

no death occurred

Clinical signs:

other: aqueous, reddish eye and nose secretion, irregular respiration, scrubby and clotted fur, hairless necrotic areas with bloody eschar. The animals were not free of symptoms at the end of the observation period (14 days).

Body weight:

male and female animals of the 16.35 mg/l dose group showed no differences compared to the control group. Male animals of the 6.64 mg/l dose group showed no differences compared to the control group. The female animals of the 6.64 mg/l dose group showed a slight weight loss after 7 days and decreased body weight gain after 14 days compared to controls.

Gross pathology:

nothing abnormal detected

Interpretation of results:

GHS criteria not met

Conclusions:

As one mol of Reaction mass of 3-hydroxypropan-1-aminium D-gluconate and N-(3-hydroxypropyl)-D-gluconamide contains 0.5 mol of 3-aminopropan-1-ol, and gluconic acid is not classified, its 4h-LC50 for inhalation of mists (aerosols) is > 5 mg/L (expected at > 8 mg/).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

No study is provided with the test article. Instead, evidence of low toxicity is based on a separate study with one of the constituents, Aminopropanol.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

No study is provided with the test article. Instead, evidence of low toxicity is based on two separate studies with one of the constituents, Aminopropanol. An SIDS report on gluconates concludes that no hazard is to be expected from dermal exposure to this substance.

Additional information

Oral exposure of rats to 3-aminopropan-1-ol showed that not more than 10% mortality was recorded at doses up to and including 1000 mg/kg, five out of 10 animals died at 1470 mg/kg and all animals died at 2150 mg/kg.

Data on acute oral toxicity for sodium gluconate in rat fed by gavage at dosages of 3000, 3600, 4320, 5190, 6210 mg/kg bw (30% (w/v) aqueous solution)potassium gluconate and observed for signs of toxicity during a 14 -day period resulted in one animal dead in the 5190 mg/kg bw group and four animals dead in the 6210 mg/kg bw group. Deaths occurred between 5 and 21 hours after treatment. Survivors recovered gradually. The LD50 was calculated (according to the method of Weil) to be 6060 mg/kg bw. However, the effects that were observed occurred at doses that exceed the accepted limit dose of 5000 mg/kg bw and thus, the LD50 may be related to high dosing. No relevant oral toxicity data were found in the literature for the other substances of the category.

Justification for classification or non-classification

As studies in rat showed a relatively low toxicity of aminopropanol with an LD50 > 1000 mg/kg and of gluconate with an LD50 value > 2000 mg/kg bw, Reaction mass of 3-hydroxypropan-1-aminium D-gluconate and N-(3-hydroxypropyl)-D-gluconamide is non-toxic with a predicted LC50 > 2000 mg/kg.