Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Oral
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Oral
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

2-phosphonobutane-1,2,4-tricarboxylic acid (CAS 37971-36-1)


Hazard conclusion systemic (worker/general population) long-term



Basis for hazard conclusion systemic effects (worker/general population):
A repeated dose toxicity study in Wistar rats (90 day feeding study) according OECD Guideline 408 is available.



There is no long-term study available using the inhalation or dermal route. Thus, as starting point for the calculation/assessment of hazard, the NOAEL of the sub-chronic feeding study has to be taken into account.
Study
Title: PBS-AM Subchronische toxikologische Untersuchungen an Ratten (Fütterungsversuch über 3 Monate)
Administration period: 90 days
Doses: 50, 200, 1000, 5000 ppm = male rats: 0, 4.17, 14.91, 84.11, 424.41 mg/kg bw/day, female rats: 0, 6.05, 12.51, 125.48, 632.65 mg/kg bw/day
NOAEL, Effects
NOAEL (systemic) = 424 mg/kg bw (male and female rats); highest dose
Effects: All doses were tolerated without any effects.
A 3-months feeding study was performed in 15 female and 15 male rats with technical tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate (CAS 66669-53-2, structural analogue, please refer to the read across justification document at IUCLID Chapter 13.2) (50, 200, 1000, 5000 ppm = male rats: 0, 4.17, 14.91, 84.11, 424.41 mg/kg bw/day, female rats: 0, 6.05, 12.51, 125.48, 632.65 mg/kg bw/day). The control animals (30 females, 30 males) received no test substance (0 ppm).
All doses were tolerated without any effects as could be shown by overall observations and examinations: Appearance, behaviour, development, and mortality as well as blood, blood glucose and cholesterol, metabolism of electrolytes (NA, K, Ca), Ferrum and Phosphorus were not affected by doses up to 5000 ppm. The same was proven for the kidneys by urinalyses, clinical chemistry and pathological and histopathological examinations. Gross necropsy and histological examinations did not reveal any adverse effects due to the test substance.
Thus, the NOAEL is equal or higher than 5000 ppm (equivalent to about 424 mg/kg bw for male rats and 632 mg/kg bw for female rats).



Additional, a developmental/teratogenicity study with 2-phosphonobutane-1,2,4-tricarboxylic acid (CAS 37971-36-1) in Wistar rats equivalent or similar to OECD Guideline 414 (Prenatal Developmental Toxicity Study) is available.
Study
Title: Untersuchung auf embryotoxische Wirkungen an Ratten nach oraler Verabreichung [Examination of embryotoxicity effects in rats following oral administration of Bayhibit-AM]
Administration period: 10 days
Doses: 0, 100, 300 or 1000 mg/kg bw/day
NOEL, Effects
NOEL (systemic) = 1000 mg/kg bw
Effects: No maternal toxicity, no teratogenicity, no embryotoxicity was observed under the study conditions.
After oral application of 2 -phosphonobutane-1,2,4 -tricarboxylic acid- up to a maximal dosage of 1000 mg/kg, no signs of maternal toxicity were found (by means of death, weight loss, changes in appearance and behaviour). Moreover, female mother rats were proved later to be fertile. No influence was observed in embryo and foetus development (resorption, placenta weight, any skeletal and internal malformation). The NOEL value for these effects is therefore determined as 1000 mg/kg bw/day.
Under the experimental conditions, the test item is considered to have no maternal and embryonic toxic effects and no teratogenic effects in rats.
Thus, the NOAEL is equal or higher than 1000 mg/kg bw.
Conclusion: In the sub-chronic study and the developmental/teratogenicity no adverse effects were observed. Therefore ‘no hazard’ is identified for systemic effects (long term).


 


Hazard conclusion systemic (worker/general population) short-term
2-phosphonobutane-1,2,4-tricarboxylic acid (CAS 37971-36-1) is not classified for acute oral, acute dermal and acute inhalation toxicity.
Conclusion: Therefore ‘no hazard’ is identified for systemic effects (short term).


 


Hazard conclusion local effects (worker/general population)
Basis for for hazard conclusion local (long- and short-term toxicity):
Irritation/corrosion
In the key studies for skin irritation/corrosion and eye irritation, the test substance (2 -phosphonobutane-1,2,4 -tricarboxylic acid) is not irritating to the skin but irritating to the eyes. Therefore a classification as Eye Irrit.2 ( H319: Causes serious eye irritation) is justified.


 


Sensitization
In a Guinea Pig maximization test (GPMT) the test substance (tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate, a structural analogue) revealed no sensitisation potential.
A classification is therefore not justified.


 


Conclusion: For local effects by inhalation the low hazard band is justified. For local dermal effects no hazard is identified.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Oral
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Oral
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Oral
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

2-phosphonobutane-1,2,4-tricarboxylic acid (CAS 37971-36-1)


DNEL systemic (worker/general population) long-term



Basis for hazard conclusion systemic effects (worker/general population):
A repeated dose toxicity study in Wistar rats (90 day feeding study) according OECD Guideline 408 is available.



There is no long-term study available using the inhalation or dermal route. Thus, as starting point for the calculation/assessment of hazard, the NOAEL of the sub-chronic feeding study has to be taken into account.
Study
Title: PBS-AM Subchronische toxikologische Untersuchungen an Ratten (Fütterungsversuch über 3 Monate)
Administration period: 90 days
Doses: 50, 200, 1000, 5000 ppm = male rats: 0, 4.17, 14.91, 84.11, 424.41 mg/kg bw/day, female rats: 0, 6.05, 12.51, 125.48, 632.65 mg/kg bw/day
NOAEL, Effects
NOAEL (systemic) = 424 mg/kg bw (male and female rats); highest dose
Effects: All doses were tolerated without any effects.
A 3-months feeding study was performed in 15 female and 15 male rats with technical tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate (CAS 66669-53-2, structural analogue, please refer to the read across justification document at IUCLID Chapter 13.2) (50, 200, 1000, 5000 ppm = male rats: 0, 4.17, 14.91, 84.11, 424.41 mg/kg bw/day, female rats: 0, 6.05, 12.51, 125.48, 632.65 mg/kg bw/day). The control animals (30 females, 30 males) received no test substance (0 ppm).
All doses were tolerated without any effects as could be shown by overall observations and examinations: Appearance, behaviour, development, and mortality as well as blood, blood glucose and cholesterol, metabolism of electrolytes (NA, K, Ca), Ferrum and Phosphorus were not affected by doses up to 5000 ppm. The same was proven for the kidneys by urinalyses, clinical chemistry and pathological and histopathological examinations. Gross necropsy and histological examinations did not reveal any adverse effects due to the test substance.
Thus, the NOAEL is equal or higher than 5000 ppm (equivalent to about 424 mg/kg bw for male rats and 632 mg/kg bw for female rats).



Additional, a developmental/teratogenicity study with 2-phosphonobutane-1,2,4-tricarboxylic acid (CAS 37971-36-1) in Wistar rats equivalent or similar to OECD Guideline 414 (Prenatal Developmental Toxicity Study) is available.
Study
Title: Untersuchung auf embryotoxische Wirkungen an Ratten nach oraler Verabreichung [Examination of embryotoxicity effects in rats following oral administration of Bayhibit-AM]
Administration period: 10 days
Doses: 0, 100, 300 or 1000 mg/kg bw/day
NOEL, Effects
NOEL (systemic) = 1000 mg/kg bw
Effects: No maternal toxicity, no teratogenicity, no embryotoxicity was observed under the study conditions.
After oral application of 2 -phosphonobutane-1,2,4 -tricarboxylic acid- up to a maximal dosage of 1000 mg/kg, no signs of maternal toxicity were found (by means of death, weight loss, changes in appearance and behaviour). No influence was observed in embryo and foetus development (resorption, placenta weight, any skeletal and internal malformation). The NOEL value for these effects is therefore determined as 1000 mg/kg bw/day.
Under the experimental conditions, the test item is considered to have no maternal and embryonic toxic effects and no teratogenic effects in rats.
Thus, the NOAEL is equal or higher than 1000 mg/kg bw.
Conclusion: In the sub-chronic study and the developmental/teratogenicity no adverse effects were observed. Therefore ‘no hazard’ is identified for systemic effects (long term).


 


Hazard conclusion systemic (worker/general population) short-term
2-phosphonobutane-1,2,4-tricarboxylic acid (CAS 37971-36-1) is not classified for acute oral, acute dermal and acute inhalation toxicity.
Conclusion: Therefore ‘no hazard’ is identified for systemic effects (short term).


 


Hazard conclusion local effects (worker/general population)
Basis for delineation of the DNELs local (long- and short-term toxicity):
Irritation/corrosion
In the key studies for skin irritation/corrosion and eye irritation, the test substance (2 -phosphonobutane-1,2,4 -tricarboxylic acid) is not irritating to the skin but irritating to the eyes. Therefore a classification as Eye Irrit.2 ( H319: Causes serious eye irritation) is justified.


 


Sensitization
In a Guinea Pig maximization test (GPMT) the test substance (tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate, a structural analogue) revealed no sensitisation potential.
A classification is therefore not justified.


 


Conclusion: For local effects by inhalation the low hazard band is justified. For local dermal effects no hazard is identified.